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Fung S. Vonoprazan: A Review in Erosive Esophagitis and Non-Erosive Gastro-Esophageal Reflux Disease. Drugs 2025:10.1007/s40265-025-02193-x. [PMID: 40388079 DOI: 10.1007/s40265-025-02193-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/17/2025] [Indexed: 05/20/2025]
Abstract
Vonoprazan (Voquezna®) is a potassium-competitive acid blocker (PCAB) with improved pharmacodynamic and pharmacokinetic properties compared with proton-pump inhibitors (PPIs) that allow for stronger control of gastric acid with once-daily oral administration and no requirement to be taken in relation to timing of meals for optimal efficacy. In the USA, vonoprazan has been approved as a first-in-class treatment for healing and maintenance of healing of erosive esophagitis, and for relief of heartburn in adult patients with erosive esophagitis and non-erosive gastro-esophageal reflux disease (GERD). In pivotal phase III trials, vonoprazan was non-inferior to the PPI lansoprazole in healing and superior to lansoprazole in maintenance of healing of erosive esophagitis, and was superior to placebo for treating heartburn in US patients with non-erosive GERD. Vonoprazan was generally well tolerated; the most common adverse events included abdominal pain, constipation, diarrhea, nausea, and dyspepsia. Vonoprazan is, therefore, a valuable addition to the therapies available for adults with erosive esophagitis and non-erosive GERD.
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Affiliation(s)
- Simon Fung
- Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
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2
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Shekeban YM, Hamdy NA, Header DA, Ahmed SM, Helmy MM. Vonoprazan-based therapy versus standard regimen for Helicobacter pylori infection management in Egypt: an open-label randomized controlled trial. Sci Rep 2025; 15:15989. [PMID: 40341536 PMCID: PMC12062291 DOI: 10.1038/s41598-025-98606-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 04/14/2025] [Indexed: 05/10/2025] Open
Abstract
As antibiotic resistance continues to rise, the development of novel H. pylori treatment regimens, combined with regular assessment of existing treatment regimens, is imperative. The study evaluates the efficacy, safety, and compliance of vonoprazan dual and triple therapy (VDT and VTT) both consisting of vonoprazan 20 mg twice daily and amoxicillin/clavulanate 875 mg/125 three times daily plus clarithromycin 500 mg twice daily added in VTT versus standard triple therapy (STT), in which vonoprazan 20 mg in VTT is replaced by PPI standard or double dose all for 14 days, along with investigating factors influencing compliance, treatment response, and symptoms severity. By per-protocol analysis, the eradication rates of the STT, VDT, and VTT groups were 70%, 76.2%, and 79.2%, respectively (p = 0.777) indicating suboptimal efficacy of the three treatment regimens. This necessitates the optimization of dosage and frequency of available treatment regimens as well as the development of new regimens with higher eradication rates. Interestingly, the VDT group demonstrated a better safety profile but with no statistically significant difference in cure rate. No difference in compliance with treatment was found between the groups. Gender, frequency of COVID-19 vaccination, height, and BMI were the only factors assessed influencing infection symptoms severity. ClinicalTrial.gov ID identifier: NCT05614934, first posted date (07/11/2022).
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Affiliation(s)
- Yumna M Shekeban
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Noha A Hamdy
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
| | - Doaa A Header
- Department of Internal Medicine, Gastroenterology and Endoscopy unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Shwikar M Ahmed
- Department of Medical Microbiology and immunology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Mai M Helmy
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
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3
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Ozercan M, Tawheed A, Ismail A, Amer MS, El-Kassas M. Vonoprazan and proton pump inhibitors: Which is superior for Helicobacter pylori eradication? World J Gastroenterol 2025; 31:103156. [DOI: 10.3748/wjg.v31.i17.103156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 02/16/2025] [Accepted: 03/12/2025] [Indexed: 04/29/2025] Open
Abstract
Helicobacter pylori is a worldwide health problem; therefore, eradicating this bacterium is important for the health and economic status of the whole world. There are a variety of anti-secretory and antibiotic combinations for this purpose; however, antibiotic resistance is a major barrier to achieving an appropriate eradication rate (> 90%). Blockage of gastric acid is the main supportive factor of the antibiotic effect on bacteria. Therefore, anti-secretory therapy with high efficacy and safety profiles should be used in eradication regimens. Vonoprazan (VPZ), a member of the potassium competitive acid blockers, is a novel agent with a potent anti-secretory effect. The present study aimed to summarize comparative and safety studies of VPZ and proton pump inhibitors (PPIs), especially the efficacy on Helicobacter pylori eradication. VPZ was reported to have a higher efficacy and safety profile in most studies that compared VPZ-based and PPI-based regimens for eradication therapy. Despite its greater cost, the effectiveness of VPZ emerges as a viable and cost-effective alternative to PPI on gastric acid-related pathologies.
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Affiliation(s)
- Mubin Ozercan
- Department of Gastroenterology, Firat University, Elazig 23119, Türkiye
| | - Ahmed Tawheed
- Department of Endemic Medicine, Helwan University, Cairo 11795, Egypt
| | - Alaa Ismail
- Faculty of Medicine, Helwan University, Cairo 11795, Egypt
| | | | - Mohamed El-Kassas
- Department of Endemic Medicine, Helwan University, Cairo 11795, Egypt
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4
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Howden CW. The Role of P-CABs in GERD. Am J Gastroenterol 2025; 120:993-998. [PMID: 39466255 DOI: 10.14309/ajg.0000000000003140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 10/11/2024] [Indexed: 10/29/2024]
Abstract
Potassium-competitive acid blockers (P-CABs) constitute a relatively new class of gastric acid-suppressing drugs. Among this class, vonoprazan is the first to have been approved in the United States. However, some P-CABs including vonoprazan, tegoprazan, and fexuprazan have been available in other countries since at least 2014. The first aim of this article is to review pharmacological differences between P-CABs that are currently approved or in development with proton pump inhibitors. The specific focus thereafter is on the likely role of P-CABs in the treatment of different manifestations of gastroesophageal reflux disease. Multiple clinical trials have compared P-CABs with proton pump inhibitors in erosive esophagitis. Additional trials have compared P-CABs with placebo in nonerosive reflux disease. Relevant results are reviewed, and inferences are drawn for their use in the United States. Finally, consideration is given to additional, potential uses of P-CABs in the broader spectrum of gastroesophageal reflux disease, and some suggestions are made for future research initiatives.
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Affiliation(s)
- Colin W Howden
- Professor Emeritus, University of Tennessee College of Medicine, Memphis, Tennessee, USA
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Baik M, Jeon J, Yoo J, Kim J. Effect of Potassium-Competitive Acid Blockers on Upper Gastrointestinal Bleeding in Patients on Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Nationwide Cohort Study. J Gastroenterol Hepatol 2025. [PMID: 40289422 DOI: 10.1111/jgh.16989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 03/16/2025] [Accepted: 04/18/2025] [Indexed: 04/30/2025]
Abstract
BACKGROUND AND AIM Proton pump inhibitors (PPIs) are the drug of choice to prevent upper gastrointestinal (UGI) bleeding in patients receiving dual antiplatelet therapy (DAPT); however, unmet needs remain. Potassium-competitive acid blockers (P-CABs) are novel acid-suppressive drugs that have emerged as potential alternatives. We evaluated the effectiveness of P-CAB in reducing the risk of UGI bleeding in patients receiving DAPT after percutaneous coronary intervention (PCI). METHODS This retrospective cohort study included patients with PCI on DAPT between January 2019 and January 2023 using the Korean nationwide health claims database. The primary outcome was admission for UGI bleeding within 6 months of PCI. A multivariate Cox regression model was used to evaluate UGI bleeding risk based on PPIs and P-CAB use. RESULTS Of the 210 447 patients who underwent PCI on DAPT (mean age, 65.5 years; 74.7% men), 4.6% and 47.5% patients were prescribed P-CABs and PPIs, respectively. Overall, 0.3% of patients experienced UGI bleeding within 6 months of PCI. P-CAB users had a reduced risk of UGI bleeding (adjusted hazard ratio, 0.59; 95% confidence interval, 0.38-0.92; p = 0.019) compared with patients not receiving P-CAB or PPI. No significant difference was observed between the P-CAB and PPI users (p > 0.05). CONCLUSIONS Among Korean patients undergoing PCI with DAPT, P-CABs reduced UGI bleeding comparably to PPIs. These findings suggest that P-CABs are potential alternatives to PPIs for preventing UGI bleeding.
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Affiliation(s)
- Minyoul Baik
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si, Gyeonggi-do, South Korea
| | - Jimin Jeon
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si, Gyeonggi-do, South Korea
| | - Joonsang Yoo
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si, Gyeonggi-do, South Korea
| | - Jinkwon Kim
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si, Gyeonggi-do, South Korea
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Zhang MM, Wang MD, Yang SY, Hu JQ, Zhu BQ, Wei YK, Zhang CL, Long EW. The efficacy and safety of vonoprazan-based high-dose dual therapy for eradication of Helicobacter pylori: A systematic review and meta-analysis. J Infect Public Health 2025; 18:102768. [PMID: 40220504 DOI: 10.1016/j.jiph.2025.102768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 03/28/2025] [Accepted: 04/03/2025] [Indexed: 04/14/2025] Open
Abstract
In order to evaluate the effectiveness and safety of high-dose dual therapy with vonoprazan for eradicating Helicobacter pylori, we searched seven electronic databases from the establishment of the database to March 2025, collecting randomized controlled clinical trials (RCTs) comparing high-dose dual therapy with vonoprazan to high-dose dual therapy with PPI and quadruple therapy with bismuth, including 13 RCTs with 4023 patients. The primary outcome is the eradication rate determined based on intention to treat analysis and protocol analysis, while secondary outcomes include incidence of adverse events and compliance. According to ITT analysis and PP treatment analysis, the eradication rates of VA therapy were 88.81 % and 93.56 %, respectively. The incidence of adverse reactions was significantly lower (14.56 % vs 26.00 %, RR=0.57, 95 % CI: 0.48-0.67, p < 0.0001), and compliance was better (96.29 % vs 93.56 %, RR=1.03, 95 % CI: 1.01-1.05, p = 0.003), making it a reliable alternative therapy.
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Affiliation(s)
- Ming-Ming Zhang
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
| | - Mei-Ding Wang
- School of Pharmacy of Southwest Medical University, Luzhou 646000, China
| | - Shi-Yu Yang
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
| | - Jia-Qiang Hu
- Department of Pharmacy, Guang'an People's Hospital, Guang'an 638000, China
| | - Bao-Qiang Zhu
- Department of Pharmacy, West China(Airport)Hospital Sichuan University, Chengdu 610200, China
| | - Yuan-Kui Wei
- School of Pharmacy of Southwest Medical University, Luzhou 646000, China
| | - Chang-Lan Zhang
- Department of Clinical Pharmacy, Jiangyou People's Hospital, Jiangyou 621700, China
| | - En-Wu Long
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; School of Pharmacy of Southwest Medical University, Luzhou 646000, China.
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Abe H, Tarasawa K, Hatta W, Tanno N, Hatayama Y, Ogata Y, Saito M, Jin X, Koike T, Imatani A, Hamada S, Fujimori K, Fushimi K, Masamune A. Which of Vonoprazan Alone or Intravenous Proton Pump Inhibitor Followed by Vonoprazan Is Optimal for Reducing Delayed Bleeding in Gastric Endoscopic Submucosal Dissection? Digestion 2025:1-10. [PMID: 40132569 PMCID: PMC12060810 DOI: 10.1159/000545253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Accepted: 03/11/2025] [Indexed: 03/27/2025]
Abstract
INTRODUCTION In gastric endoscopic submucosal dissection (ESD), both vonoprazan alone and intravenous proton pump inhibitor (PPI) followed by vonoprazan have lower delayed bleeding risk than PPI alone. This study aimed to clarify an optimal acid-suppressive method in gastric ESD. METHODS This population-based cohort study included patients who underwent gastric ESD on only vonoprazan (vonoprazan alone group) or intravenous PPI followed by vonoprazan (intravenous PPI group) using the Diagnosis Procedure Combination database in Japan between 2014 and 2021. The primary outcome was delayed bleeding. To balance the two comparison groups, propensity score matching (PSM), based on 18 variables, was performed; subsequently, to compare the bleeding outcome, logistic regression analysis was performed. RESULTS Of 63,952 patients, 24,710 pairs were compared following PSM. The delayed bleeding risk in the vonoprazan alone group was similar to that in the intravenous PPI group (odds ratio [OR], 1.00; 95% confidence interval, 0.93-1.08; delayed bleeding rate, 5.9% vs. 5.9%). The results were consistent in some sensitivity and subgroup analyses; however, the result was modified by the status of antithrombotic agents (p for interaction = 0.029). In additional analyses, in patients with antithrombotic agent, the vonoprazan alone group had a higher delayed bleeding risk than the intravenous PPI group (OR, 1.15). CONCLUSION Both vonoprazan alone and intravenous PPI followed by vonoprazan might be acceptable in gastric ESD when antithrombotic agents were not administered, whereas intravenous PPI followed by vonoprazan might be favorable in patients with antithrombotic agents.
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Affiliation(s)
- Hiroko Abe
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kunio Tarasawa
- Department of Health Administration and Policy, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Waku Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Naotaro Tanno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yutaka Hatayama
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yohei Ogata
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Masahiro Saito
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Xiaoyi Jin
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Akira Imatani
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Shin Hamada
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kenji Fujimori
- Department of Health Administration and Policy, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
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Li X, Jiang C, Su Y, Gao R, Yang P, Qin Y, Zou Y, Liang W, Quan J, Pan L. Efficacy and safety of vonoprazan-amoxicillin dual therapy versus bismuth-containing quadruple therapy for patients with Helicobacter pylori infection: a meta-analysis. Front Microbiol 2025; 16:1561749. [PMID: 40177490 PMCID: PMC11962034 DOI: 10.3389/fmicb.2025.1561749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 03/04/2025] [Indexed: 04/05/2025] Open
Abstract
Introduction This meta-analysis aims to compare the efficacy and safety of vonoprazan-amoxicillin (VA) dual therapy in comparison to bismuth-containing quadruple therapy (BQT) for patients with Helicobacter pylori (H. pylori) infection. Materials and methods Four databases (PubMed, Embase, Web of Science, and Cochrane Library) were searched published from establishment of database to June 1, 2024, for articles studying VA dual therapy compared to BQT for patients with H. pylori infection. Meta-analyses of eradication rates, adverse events, compliance and cost were preformed. Results A total of 17 studies were included for meta-analysis. Compared with BQT, VA increased the incidence of H. pylori eradication rate, with significant difference under the ITT analysis (86.9% vs. 80.4%, RR = 1.07, 95% CI: 1.01-1.12, p = 0.01) but there no significant difference under the PP analysis (90.7% vs. 86.5%, RR = 1.03, 95% CI: 0.99-1.08, p = 0.13). Besides, VA significantly increased compliance (RR = 1.03, 95% CI: 1.01-1.05, p < 0.01) and decreased the occurrence of total adverse events (27.0% vs. 11.5%, RR = 0.43, 95% CI: 0.37-0.51, p < 0.01). Furthermore, VA has lower cost compared to BQT. Conclusion Our findings indicated that VA dual therapy provided a higher eradication rate, enhanced compliance, decreased adverse events, and lowered cost relative to BQT for patients with H. pylori infection. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024576738, identifier CRD42024576738 (PROSPERO).
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Affiliation(s)
- Xiao Li
- The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, China
| | - Cheng Jiang
- The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, China
| | - Yuwen Su
- Lingui Campus, Guilin Medical University, Guilin, Guangxi, China
| | - Ruiyun Gao
- The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, China
| | - Peijun Yang
- The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, China
| | - Yuechen Qin
- The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, China
| | - Yue Zou
- The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, China
| | - Weiming Liang
- The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, China
| | - Jieru Quan
- School of Economics and Management, Guangxi University of Science and Technology, Liuzhou, Guangxi, China
| | - Liying Pan
- The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, China
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Yoon IM, Kim KY, Lee KH, Yoo DW, Oh H. Efficacy of Potassium-Competitive Acid Blockers Versus Proton Pump Inhibitors for Gastric Ulcers: Bayesian and Frequentist Network Meta-Analysis With Cross-Inference Through a Quality management System. CURRENT THERAPEUTIC RESEARCH 2025; 102:100776. [PMID: 40092642 PMCID: PMC11910678 DOI: 10.1016/j.curtheres.2025.100776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 01/30/2025] [Indexed: 03/19/2025]
Abstract
Purpose Proton pump inhibitors (PPIs) have been the mainstay treatment for gastric ulcer (GU) for over 30 years. However, since the discovery of a new class of acid suppressants, potassium-competitive acid blockers (P-CABs), the desire for a therapeutic agent has continued and the clinical trials on P-CABs have been conducted. In this regard, we aimed to assess whether P-CABs are noninferior to PPIs in patients with GU in terms of efficacy. Methods We performed a systematic review and network meta-analysis (NMA) based on randomized controlled trials (RCTs). Additionally, we used a new methodology of inference concept with the purpose of grouping between P-CABs and PPIs. Moreover, our quality management system was integrated throughout the research to ensure data accuracy. Findings We initially screened 438 studies and extracted 10 homogeneous GU RCTs with 6315 participants. The odds ratios (ORs) for the 4-week cure rate in Bayesian + frequentist NMA, tegoprazan 100 mg (OR = 4.14, 95% credible interval [CI] 0.56-26.3) and pantoprazole 40 mg (OR = 4.12, 95% CI 1.90-8.88) were the largest, respectively. The ORs for the 8-week cure rate in Bayesian + frequentist NMA, lansoprazole 30 mg (OR = 8.77, 95% credible interval [CI] 0.95-78.9) and lansoprazole 30 mg (OR = 7.91, 95% CI 2.60-24.03) was the largest, respectively. Conclusions The results of the NMA reveal that the cure rates of P-CABs in cases of GU were not inferior to those of PPIs. As the inference by grouping PPIs and P-CABs, the results showed similar trends in terms of effectiveness between the two therapeutic classes.
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Affiliation(s)
- In Mo Yoon
- Unimedi Plastic Surgery Clinic, Gangnam-gu, Seoul, Republic of Korea
| | - Kang-Yon Kim
- Yonsei Da-on Family Medicine Clinic, Seosan, Chungcheongnam-do, Republic of Korea
| | - Kwan-Haeng Lee
- Sokpyunhan Internal Medicine Clinic, Seosan, Chungcheongnam-do, Republic of Korea
| | - Duk-Woo Yoo
- Chung-Ang Herb Dental Clinic, Seosan, Chungcheongnam-do, Republic of Korea
| | - Hojin Oh
- Oh Medicine and Methodology Research Institute, Seosan, Chungcheongnam-do, Republic of Korea
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10
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Zhu B, Chen L, Tao X, Zheng H, Li X, Wu Q, Long E, Lin H. Current research status and trends of potassium-competitive acid blockers in the treatment of acid-related diseases: a bibliometric analysis. Front Pharmacol 2025; 15:1477633. [PMID: 39840081 PMCID: PMC11747516 DOI: 10.3389/fphar.2024.1477633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 12/16/2024] [Indexed: 01/23/2025] Open
Abstract
Objective To explore the current research status and trends of potassium-competitive acid blockers (P-CABs) in the treatment of acid related diseases (ARDs) using bibliometric analysis. Materials and methods We collected publications related to P-CAB in the treatment of acid-related diseases in the Web of Science (WOS) Core Collection from the establishment of the database to 30 June 2024. We evaluated the publication volume and citation status over the years using the WOS platform, and visualized the authors, countries, institutions, keywords, and citations of the publications using CiteSpace and VOSviewer. Results This study included a total of 455 articles. The number of publications and citations related to research has been increasing year by year. The results show that the scholars with the highest number of publications mainly come from South Korea and Japan. Scholars such as Geun Seog Song, Bongtae Kim, and Nobuhiro Inatomi produced many works in related fields. The most popular drug in this field was vonoprazan, and research on this drug mainly focused on the effectiveness and safety evaluation of ARDs such as Helicobacter pylori infection, gastroesophageal reflux disease, peptic ulcers, etc. Researchers were concerned about the evaluation of treatment regimens and efficacy comparison between P-CABs and traditional proton pump inhibitors (PPIs) in the treatment of ARDs. At the same time, researchers are also closely monitoring the potential adverse reactions and long-term adverse outcomes of clinical application of P-CABs for ARDs. Conclusion The clinical application of P-CABs, represented by vonoprazan, in ARDs is receiving widespread attention from researchers. The exploration of the application of this type of drug in ARDs is constantly expanding, and it is a research field with great clinical value and research potential.
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Affiliation(s)
- Baoqiang Zhu
- Department of Pharmacy, The First People’s Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, China
| | - Long Chen
- Department of Pharmacy, The First People’s Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, China
| | - Xue Tao
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Hong Zheng
- Department of Pharmacy, The First People’s Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, China
| | - Xia Li
- Department of Pharmacy, The First People’s Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, China
| | - Qingfang Wu
- Department of Pharmacy, The First People’s Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, China
| | - Enwu Long
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Haixia Lin
- Department of Pharmacy, The First People’s Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, China
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Kang SH, Moon HS, Sung JK, Kim SM, Kim KB, Lee SW, Cho YS, Bang KB, Song KH. Assessment of the efficacy of on-demand tegoprazan therapy in gastroesophageal reflux disease through a randomized controlled trial. Sci Rep 2025; 15:168. [PMID: 39748010 PMCID: PMC11697203 DOI: 10.1038/s41598-024-84065-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 12/19/2024] [Indexed: 01/04/2025] Open
Abstract
In patients with gastroesophageal reflux disease (GERD) whose symptoms improve with acid-suppression therapy, on-demand treatment could constitute maintenance therapy. This study investigated the comparative efficacy and safety of on-demand tegoprazan and proton-pump inhibitor (PPI) therapy in GERD. From six university hospitals in the Daejeon-Chungcheong region, we enrolled patients with GERD who had experienced symptomatic improvement with acid-suppressive therapy and, using a randomization table, randomly allocated these participants to two groups: to receive either tegoprazan 50 mg + esomeprazole placebo or tegoprazan placebo + esomeprazole 20 mg, respectively. The primary endpoint of this study was the intergroup difference in patient satisfaction with on-demand therapy. Among the 69 participants who completed 8 weeks of on-demand therapy and rated patient satisfaction on a 5-point Likert scale, the tegoprazan and esomeprazole groups scored an average of 4.31 and 4.15 points, respectively, without any significant intergroup difference. In the tegoprazan group, 26.2% (182/694) of those with episodes experienced symptom improvement within 30 min, which is a significantly higher proportion compared to 16.1% (104/646) in the esomeprazole group. Compared to the esomeprazole group, the tegoprazan group had a significantly shorter time to symptom improvement overall and a significantly higher proportion of patients who improved within 30 min. No serious treatment-emergent adverse events were reported. Tegoprazan is effective as on-demand therapy for GERD and offers the expectation of faster symptom improvement than with PPIs. Clinical trial KCT0009296, registered at cris.nih.go.kr.
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Affiliation(s)
- Sun Hyung Kang
- Department of Gastroenterology, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Hee Seok Moon
- Department of Gastroenterology, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Jae Kyu Sung
- Department of Gastroenterology, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Sun Moon Kim
- Department of Gastroenterology, College of Medicine, Konyang University, Daejeon, Republic of Korea.
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon, Republic of Korea.
| | - Ki Bae Kim
- Department of Gastroenterology, Chungbuk National University College of Medicine, Cheong-Ju, Republic of Korea
| | - Seung Woo Lee
- Department of Gastroenterology, Catholic University of Korea School of Medicine, Daejeon, Republic of Korea
| | - Young Sin Cho
- Department of Gastroenterology, College of Medicine, Soonchunhyang University, Cheong-Ju, Republic of Korea
| | - Ki Bae Bang
- Department of Gastroenterology, College of Medicine, Dankook University, Cheong-Ju, Republic of Korea
| | - Kyung Ho Song
- Department of Gastroenterology, CHA Ilsan Medical Center, Ilsan, Republic of Korea
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Shin CM, Choi SC, Cho JW, Kim SY, Lee OJ, Kim DH, Cho YK, Lee JY, Lee SK, Shin JE, Kim GH, Park S, Hong SJ, Jung H, Lee SJ, Youn YH, Jeon SW, Sung IK, Park MI, Lee OY. Comparison of Tegoprazan and Lansoprazole in Patients With Erosive Esophagitis up to 4 Weeks: A Multi-Center, Randomized, Double-Blind, Active-Comparator Phase 4 Trial. Neurogastroenterol Motil 2025; 37:e14969. [PMID: 39587796 PMCID: PMC11650551 DOI: 10.1111/nmo.14969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 10/23/2024] [Accepted: 11/13/2024] [Indexed: 11/27/2024]
Abstract
BACKGROUND The aims of this study were to confirm the non-inferiority of tegoprazan to lansoprazole up to week 4 in patients with erosive esophagitis (EE) and to evaluate its effectiveness in rapid mucosal healing and symptom relief at week 2. METHODS In this multi-center, randomized, double-blind, active-comparator non-inferiority trial, 218 patients with endoscopically confirmed EE (Los Angeles Classification Grades A-D) were randomly allocated to either the tegoprazan (50 mg) or lansoprazole (30 mg) group. The primary endpoint was the cumulative proportion of patients with healed EE up to week 4, as confirmed through endoscopy. The proportion of patients with healed EE at week 2 was also evaluated. Furthermore, CYP2C19 genotypes, symptoms, safety, and tolerability were assessed. KEY RESULTS In the full-analysis set, 103 and 109 participants in the tegoprazan and lansoprazole groups, respectively, were analyzed. The cumulative healing rates up to week 4 were 95.2% (98/103) and 86.2% (94/109) (difference [95% confidence interval], 8.91 [1.22-16.59]; p < 0.0001 for non-inferiority and 0.0266 for superiority), while those at week 2 were 88.4% (91/103) and 82.6% (90/109) (5.78 [-3.66-15.22], p = 0.0005 for non-inferiority) for tegoprazan and lansoprazole, respectively. Tegoprazan showed consistent healing rates regardless of CYP2C19 genotypes. CONCLUSIONS AND INFERENCES Tegoprazan was superior to lansoprazole in the treatment of EE up to 4 weeks. Further studies are necessary to confirm these findings and clarify the superiority of tegoprazan, especially in the treatment of severe EE. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT05267743.
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Affiliation(s)
- Cheol Min Shin
- Department of Internal MedicineSeoul National University Bundang HospitalSeongnamKorea
| | - Suck Chei Choi
- Department of Gastroenterology, School of MedicineWonkwang UniversityIksanKorea
| | - Jin Woong Cho
- Department of Internal MedicinePresbyterian Medical CenterJeonjuKorea
| | - Seung Young Kim
- Department of GastroenterologyKorea University Ansan HospitalAnsanKorea
| | - Ok Jae Lee
- Department of Internal MedicineGyeongsang National University HospitalJinjuKorea
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
| | - Yu Kyung Cho
- Department of Internal MedicineThe Catholic University of Korea Seoul St. Mary's HospitalSeoulKorea
| | - Ju Yup Lee
- Department of Internal MedicineKeimyung University Dongsan HospitalDaeguKorea
| | - Sang Kil Lee
- Department of Gastroenterology, Severance HospitalYonsei University College of MedicineSeoulKorea
| | - Jeong Eun Shin
- Department of GastroenterologyDankook University HospitalCheonanKorea
| | - Gwang Ha Kim
- Department of Internal MedicinePusan National University College of Medicine, and Biomedical Research Institute, Pusan National University HospitalBusanKorea
| | - Seon‐Young Park
- Department of GastroenterologyChonnam National University HospitalGwangjuKorea
| | - Su Jin Hong
- Department of Internal MedicineSoonchunhyang University Bucheon HospitalBucheonKorea
| | - Hye‐Kyung Jung
- Department of Internal MedicineCollege of Medicine, Ewha Womans UniversitySeoulKorea
| | - Sang Jin Lee
- Department of Internal Medicine, Gangneung Asan HospitalUniversity of Ulsan College of MedicineGangneungKorea
| | - Young Hoon Youn
- Department of Gastroenterology, Gangnam Severance HospitalYonsei University College of MedicineSeoulKorea
| | - Seong Woo Jeon
- Department of GastroenterologyKyungpook National University Chilgok HospitalDaeguKorea
| | - In Kyung Sung
- Department of Internal MedicineKonkuk University Medical CenterSeoulKorea
| | - Moo In Park
- Department of GastroenterologyKosin University Gospel HospitalBusanKorea
| | - Oh Young Lee
- Department of Internal MedicineHanyang University College of MedicineSeoulKorea
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13
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Howden CW, Scarpignato C, Leifke E, Mulford DJ, Lahu G, Facius A, Yuan Y, Hunt R. Mathematical model of the relationship between pH holding time and erosive esophagitis healing rates. CPT Pharmacometrics Syst Pharmacol 2025; 14:28-41. [PMID: 39297248 PMCID: PMC11706433 DOI: 10.1002/psp4.13235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 08/22/2024] [Accepted: 08/30/2024] [Indexed: 01/11/2025] Open
Abstract
Effective suppression of gastric acid secretion promotes healing of erosive esophagitis. Treatment guidelines recommend proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs). Emerging evidence also supports potassium-competitive acid blockers (P-CABs). The aim was to construct a mathematical model to examine the relationship between pH holding time ratios (HTRs) and erosive esophagitis healing rates with H2RAs, PPIs and P-CABs. By literature search, we identified studies of H2RAs, PPIs or P-CABs that reported mean pH >4 HTRs at steady state (days 5-8) and erosive esophagitis healing rates after 4 and/or 8 weeks. We aggregated treatments by drug class and developed a non-linear, mixed-effects model to explore the relationship between pH >4 HTRs and healing rates. The pH dataset included 82 studies (4297 participants; 201 dosage arms); healing rate data came from 103 studies (43,417 patients; 196 treatment arms). P-CABs achieved the longest periods with intragastric pH >4, and the highest healing rates after 4 and 8 weeks. The predicted probabilities of achieving ≥90% healing rates at 8 weeks were 74.1% for P-CABs, 17.3% for PPIs and 0% for H2RAs. P-CABs provide the longest duration with intragastric pH >4 and, accordingly, the highest healing rates of erosive esophagitis.
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Affiliation(s)
- Colin W. Howden
- University of Tennessee College of MedicineMemphisTennesseeUSA
| | | | - Eckhard Leifke
- Phathom PharmaceuticalsResearch and DevelopmentBuffalo GroveIllinoisUSA
| | - Darcy J. Mulford
- Phathom PharmaceuticalsResearch and DevelopmentBuffalo GroveIllinoisUSA
| | | | | | - Yuhong Yuan
- Division of Gastroenterology, Department of MedicineMcMaster UniversityHamiltonOntarioCanada
- Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamiltonOntarioCanada
| | - Richard Hunt
- Division of Gastroenterology, Department of MedicineMcMaster UniversityHamiltonOntarioCanada
- Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamiltonOntarioCanada
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14
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Jankovic K, Gralnek IM, Awadie H. Emerging Long-Term Risks of the Use of Proton Pump Inhibitors and Potassium-Competitive Acid Blockers. Annu Rev Med 2025; 76:143-153. [PMID: 39536076 DOI: 10.1146/annurev-med-050223-112834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Acid-related disorders represent a significant global health burden. Pharmacological treatment of these conditions has at times been challenged and limited by incomplete effectiveness, antibiotic resistance, adverse medication effects and/or interactions, and disease recurrence. Since the early 1990s, the mainstay of treatment has been proton pump inhibitors (PPIs). Recently, the US Food and Drug Administration issued a clearance for vonoprazan, a potassium-competitive acid blocker (PCAB). PCABs are a new class of acid-suppressing agents that may overcome some of these challenges. The aim of this review is to evaluate and compare the emerging long-term risks of PPI and PCAB therapies.
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Affiliation(s)
- Katarina Jankovic
- Clinic for Gastroenterohepatology, University Clinical Centre of Serbia, Belgrade, Serbia
| | - Ian M Gralnek
- Ellen and Pinchas Mamber Institute of Gastroenterology and Hepatology, Emek Medical Center, Afula, Israel;
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Halim Awadie
- Ellen and Pinchas Mamber Institute of Gastroenterology and Hepatology, Emek Medical Center, Afula, Israel;
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15
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Tietto A, Faggin S, Scarpignato C, Savarino EV, Giron MC. Safety of potassium-competitive acid blockers in the treatment of gastroesophageal reflux disease. Expert Opin Drug Metab Toxicol 2025; 21:53-68. [PMID: 39189409 DOI: 10.1080/17425255.2024.2397433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 07/13/2024] [Accepted: 08/23/2024] [Indexed: 08/28/2024]
Abstract
INTRODUCTION Proton pump inhibitors (PPIs) are the first-line treatment for gastroesophageal reflux disease (GERD). However, due to their intrinsic limitations, there are still unmet clinical needs that have fostered the development of potassium-competitive acid blockers (P-CABs). Currently, four different drugs (vonoprazan, tegoprazan, fexuprazan, and keverprazan) are marketed in some Asian countries, whereas only vonoprazan and tegoprazan are available in Western countries (USA and Brazil or Mexico, respectively). AREAS COVERED This review summarizes the current knowledge on P-CABs acute and long-term safety in GERD treatment compared to that of PPIs. Full-text articles and abstracts were searched in PubMed. EXPERT OPINION P-CABs proved to address some of the unmet clinical needs in GERD, with a favorable risk-benefit ratio compared to conventional PPIs. Preclinical and clinical findings have highlighted P-CAB safety to be superimposable, to that of PPIs, in short-term treatments, although further studies are warranted to monitor their effects in long-term therapy. From an epidemiological point of view, the paucity of rigorous data for many variables (e.g. age, ethnicity, drug interactions, comorbidities, genetic polymorphisms, interindividual susceptibility, and gut dysbiosis) deserves a worldwide framework of continuous pre/post-marketing pharmacovigilance programs to reduce potential confounding factors and accurately link acute and chronic P-CAB therapy to adverse outcomes.
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Affiliation(s)
- Angela Tietto
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
- School of Specialization in Clinical Pharmacology and Toxicology, University of Ferrara, Ferrara, Italy
| | - Sofia Faggin
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Carmelo Scarpignato
- Department of Health Sciences, United Campus of Malta, Msida, Malta
- Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
| | | | - Maria Cecilia Giron
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
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16
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Marabotto E, Calabrese F, Pasta A, Visaggi P, de Bortoli N, Mari A, Tolone S, Ghisa M, Bertin L, Savarino V, Savarino EV. Evaluating Vonoprazan for the treatment of erosive GERD and heartburn associated with GERD in adults. Expert Opin Pharmacother 2024; 25:2319-2325. [PMID: 39503620 DOI: 10.1080/14656566.2024.2427335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Accepted: 11/05/2024] [Indexed: 11/12/2024]
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is a common debilitating chronic disease presenting in two main forms based on esophageal mucosal appearance, the erosive reflux disease (ERD) and the non-erosive reflux disease (NERD). Acid secretion is a key factor in the disease pathogenesis and management. Potent acid-suppressant drugs have been manufactured since the mid of 1970s, initially with histamine-H2-receptors antagonists, and later, inhibitors of the proton pump (H+-K+-ATPase).More recently, potassium-competitive acid blockers (p-CABs), particularlyVonoprazan, have been introduced. Vonoprazan has shown high efficacy and safety profiles and exhibits several advantages that allow to overcome shortcomings of proton pump inhibitors (PPIs). AREAS COVERED In this review, we provide an updated summary of Vonoprazan pharmacodynamics and its role in clinical practice for the management of erosive esophagitis and GERD-related heartburn. Moreover, we discuss characteristics of Vonoprazan that allow to bypass some limitations of the older PPIs. EXPERT OPINION Long-term safety and efficacy of Vonoprazan have already been demonstrated for the induction and maintenance of ERD, preventing nocturnal acid breakthrough, reducing reflux symptoms in non-responder to standard therapy. Ongoing and future studies are expected to further elucidate its long-term benefits and potential applications in other acid-related disorders.
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Affiliation(s)
- Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Francesco Calabrese
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Andrea Pasta
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Amir Mari
- Gastroenterology Unit, Nazareth Hospital EMMS, Azrieli Faculty of Medicine, Bar Ilan University, Ramat Gan, Israel
| | - Salvatore Tolone
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Matteo Ghisa
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale Università Padova, Padova, Italy
| | - Luisa Bertin
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale Università Padova, Padova, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Edoardo Vincenzo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale Università Padova, Padova, Italy
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Lin A, Lin Z, Liu Y, Chen S, Shao Y, Qiu F, Xiao Z, Xu Z, Chen L, Chen L, Lin W, Wang Y, Huang Z, Lin Z, Huang X. Ten-day versus 14-day vonoprazan-amoxicillin high-dose dual therapy for Helicobacter pylori eradication in China: A multicenter, open-label, randomized study. J Gastroenterol Hepatol 2024; 39:2645-2653. [PMID: 39582213 DOI: 10.1111/jgh.16761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 09/03/2024] [Accepted: 09/24/2024] [Indexed: 11/26/2024]
Abstract
BACKGROUND AND AIM Only a few studies have investigated the efficacy and safety of different durations of vonoprazan and amoxicillin (VA) high-dose dual therapy for the eradication of Helicobacter pylori. We aimed to compare the efficacy and safety of 10 days versus 14 days of VA high-dose dual therapy for H. pylori eradication. METHODS This study was conducted in 14 centers in China. A total of 250 patients infected with H. pylori were randomly assigned to Group VA-10 or VA-14. Both groups received the VA dual therapy (vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily). The primary endpoint was the H. pylori eradication rate. Secondary endpoints included adverse events and patient compliance. RESULTS Group VA-10 achieved eradication rates of 89.60%, 91.06%, and 91.67% as determined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analysis, respectively. The eradication rates were similar to those in Group VA-14: 91.20%, 93.44%, and 93.39%. The difference and 90% confidence interval boundary -1.60% (-7.73% to 4.53%) in the ITT analysis, -2.39% (-8.00% to 3.23%) in the MITT analysis, and -1.72% (-7.29% to 3.85%) in the PP analysis were greater than the predefined noninferiority margin of -10%, establishing a noninferiority of Group VA-10 versus Group VA-14 (noninferiority P = 0.001 in ITT analysis, P < 0.001 in MITT analysis, and P < 0.001 in PP analysis, respectively). No significant differences were observed in adverse events between the two groups. CONCLUSIONS Ten-day VA dual therapy achieves comparable efficacy and safety to the 14-day regimen in Chinese population, providing patients with greater convenience and economic benefits.
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Affiliation(s)
- Aiping Lin
- Department of Gastroenterology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, China
| | - Zhihui Lin
- Department of Gastroenterology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, China
| | - Yijuan Liu
- Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Shuo Chen
- Department of Gastroenterology, Nanping People's Hospital, Nanping, China
| | - Yanfeng Shao
- Department of Gastroenterology, The Third People's Hospital of Fujian Province, Fuzhou, China
| | - Feng Qiu
- Department of Gastroenterology, Fujian Provincial Hospital North Brance Fujian Provincial Geriatric Hospitals, Fuzhou, China
| | - Zhongqin Xiao
- Department of Gastroenterology, Nanping Second Hospital, Nanping, China
| | - Zhangkun Xu
- Department of Gastroenterology, The General Hospital of Fujian Energy Group, Fuzhou, China
| | - Longqun Chen
- Department of Gastroenterology, Jinjiang Second Hospital (Jinjiang Anhai Hospital), Quanzhou, China
| | - Lianghuo Chen
- Department of Gastroenterology, Anxi Country Hospital, Quanzhou, China
| | - Weixing Lin
- Department of Gastroenterology, Fuding City Hospital, Ningde, China
| | - Yongfu Wang
- Department of Gastroenterology, Liancheng Hospital, Longyan, China
| | - Zhonghua Huang
- Department of Gastroenterology, Putian First Hospital, Putian, China
| | - Zhenqun Lin
- Department of Gastroenterology, Zhangzhou Municipal Hospital of TCM, Zhangzhou, China
| | - Xueping Huang
- Department of Gastroenterology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, China
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Bunchorntavakul C, Jaigla P. Efficacy of Vonoprazan 10 mg and 20 mg for Patients With Proton Pump Inhibitor-Refractory Functional Dyspepsia: A Double-Blinded, Randomized Study. JGH Open 2024; 8:e70082. [PMID: 39713745 PMCID: PMC11659636 DOI: 10.1002/jgh3.70082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 11/27/2024] [Accepted: 12/09/2024] [Indexed: 12/24/2024]
Abstract
Background A proportion of patients with functional dyspepsia (FD) have inadequate symptom control with proton pump inhibitors (PPIs) treatment. Vonoprazan demonstrates higher efficacy in acid reduction than PPI; however, the existing efficacy data for vonoprazan in treating PPI-refractory FD is limited. Methods This double-blinded, randomized controlled trial study was conducted at Rajavithi Hospital, Bangkok between December 2022 and 2023. Patients with FD who were unresponsive to the standard dose PPI were randomly assigned (1:1) to receive either 10 mg or 20 mg of vonoprazan for a 4-week duration, with a subsequent 4-week follow-up after treatment. The primary outcome was changes in the Global Overall Symptoms Scale (GOSS). Results Sixty patients were randomized without significant differences in baseline characteristics between both groups. The mean GOSS between the 10-mg vonoprazan and the 20-mg vonoprazan arm were 25.73 and 26.17 at week 0, 14.33 and 15.50 at week 2, 9.37 and 10.04 at week 4, and 9.79 and 9.33 at week 8, respectively (all p < 0.001 vs. baseline and p > 0.05 between groups). The quality of life was improved, with the Nepean dyspepsia index changing -4.13 and -4.25 at week 4, respectively (all p < 0.001 vs. baseline; p = 0.853 between groups). Symptom response rates (> 50% improvement in GOSS) were 72.4% and 75.9% at week 8, respectively (p = 0.24 between groups). No serious adverse events were observed. Conclusion Vonoprazan demonstrated significant effects in the alleviation of symptoms in PPI-refractory FD patients. There was no statistically significant difference in symptom alleviation between the 10 mg and 20 mg doses of vonoprazan.
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Affiliation(s)
- Chalermrat Bunchorntavakul
- Division of Gastroenterology and Hepatology, Rajavithi Hospital, College of MedicineRangsit UniversityBangkokThailand
| | - Pantaree Jaigla
- Division of Gastroenterology and Hepatology, Rajavithi Hospital, College of MedicineRangsit UniversityBangkokThailand
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Yang E, Hwang I, Ji SC, Kim J, Lee S. Population pharmacokinetic analysis of zastaprazan (JP-1366), a novel potassium-competitive acid blocker, in patients and healthy volunteers. CPT Pharmacometrics Syst Pharmacol 2024; 13:2150-2158. [PMID: 39268835 DOI: 10.1002/psp4.13228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 08/04/2024] [Accepted: 08/07/2024] [Indexed: 09/15/2024] Open
Abstract
Zastaprazan (JP-1366) is a novel potassium-competitive acid blocker for the treatment of acid-related disorders. We aimed to establish a population pharmacokinetic (PK) model of zastaprazan, thereby characterizing the PK of zastaprazan in patients with gastroesophageal reflux disease (GERD) as well as evaluating the impact of various covariates, including CYP2C19 phenotypes, on zastaprazan PK. This population PK analysis included zastaprazan plasma concentration-time data from 92 patients with erosive GERD and 68 healthy volunteers without any gastrointestinal disorders and was performed using nonlinear mixed-effect modeling. Simulations were conducted to predict zastaprazan PK under various dosing regimens in patients with GERD. The plasma PK of zastaprazan was adequately described by a two-compartment model with Erlang-type absorption (six sequential compartments) and first-order elimination. CYP2C19 phenotypes had no significant effect on zastaprazan PK. The disease status was identified as a significant covariate on apparent clearance of zastaprazan, showing lower values in patients with GERD compared to healthy volunteers. However, the model-based simulation indicated that the impact of disease status on zastaprazan exposure was not clinically meaningful. Overall, the current population PK model successfully characterized the observed zastaprazan PK in both patients with GERD and healthy volunteers.
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Affiliation(s)
- Eunsol Yang
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea
| | - Inyoung Hwang
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea
| | - Sang Chun Ji
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea
| | - John Kim
- Onconic Therapeutics Inc., Seoul, Korea
| | - SeungHwan Lee
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea
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Kim SI, Lee YC, Cha W, Jung AR, Jang JY, Choi JS, Lee DK, Lee HH, Kwon MS, Lee YS, Eun YG. Efficacy and safety of fexuprazan in patients with symptoms and signs of laryngopharyngeal reflux disease: a randomized clinical trial. Eur Arch Otorhinolaryngol 2024; 281:5873-5883. [PMID: 39115573 DOI: 10.1007/s00405-024-08877-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 07/26/2024] [Indexed: 10/28/2024]
Abstract
PURPOSE Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD. METHODS This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events. RESULTS A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p = .036 and .045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough. CONCLUSION Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI. TRIAL REGISTRATION KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100 .
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Affiliation(s)
- Su Il Kim
- Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University School of Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Korea
| | - Young Chan Lee
- Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University School of Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Korea
| | - Wonjae Cha
- Department of Otorhinolaryngology-Head & Neck Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Ah Ra Jung
- Department of Otolaryngology-Head and Neck Surgery, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea
| | - Jeon Yeob Jang
- Department of Otolaryngology, Ajou University School of Medicine, Suwon, Korea
| | - Jeong-Seok Choi
- Department of Otorhinolaryngology-Head and Neck Surgery, Inha University College of Medicine, Incheon, Korea
| | - Dong Kun Lee
- Department of Otorhinolaryngology, Head and Neck Surgery, Dong-A University College of Medicine, Busan, Korea
| | - Hwan Ho Lee
- Department of Otolaryngology-Head and Neck Surgery, Kosin University College of Medicine, Busan, Korea
| | - Min Su Kwon
- Department of Otolaryngology-Head and Neck Surgery, Asan Medical Center, College of Medicine, University of Ulsan, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea
| | - Yoon Se Lee
- Department of Otolaryngology-Head and Neck Surgery, Asan Medical Center, College of Medicine, University of Ulsan, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea.
| | - Young-Gyu Eun
- Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University School of Medicine, Kyung Hee University Medical Center, 23 Kyungheedae-Ro, Dongdaemun-Gu, Seoul, 02447, Korea.
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Cheng Y, Yang L, Xu S, Zhang C. Vonoprazan is Not Inferior to Proton Pump Inhibitors in Bismuth-containing Quadruple Therapy for Helicobacter pylori Eradication : A Meta-analysis of 10 Studies From East Asia. J Clin Gastroenterol 2024; 58:950-956. [PMID: 38607993 DOI: 10.1097/mcg.0000000000002001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/14/2024]
Abstract
OBJECTIVE To investigate the efficacy and safety of vonoprazan based bismuth-containing quadruple therapy (VBCQ) in eradicating Helicobacter pylori ( Hp ). MATERIALS AND METHODS The VBCQ and the proton pump inhibitor-based bismuth-containing quadruple regimen (PBCQ) were compared by retrieving relevant studies in Pubmed, Embase, Cochrane Library, CNKI, and Wanfang data. Combined analysis was performed with risk ratio (RR) and 95% CI as effect values. RESULTS A total of 10 studies were enrolled, including 7 randomized controlled trials and 3 cohort studies. In intention-to-treat analysis, the eradication rate of VBCQ (89.24%, 1103/1236) was significantly higher than that of PBCQ (84.03%, 1021/1215), with RR = 1.06 (95% CI: 1.03~1.10). In per-protocol analysis, the eradication rates of VBCQ and PBCQ were 92.94% (895/963) and 87.82% (829/944), respectively, with a significant difference (RR = 1.06, 95% CI: 1.03~1.09). Subgroup analysis of study design types shared similar results. VBCQ and PBCQ showed an incidence of adverse reactions of 37.30% (304/815) and 34.94% (282/807), respectively. Significant differences were not found between the two groups (RR = 1.07, 95% CI: 0.96-1.19), nor in subgroup analysis. The good compliance rates in VBCQ and PBCQ groups were 94.32% (216/229) and 95.13% (215/226), respectively, with no significant difference (RR = 0.99, 95% CI: 0.95~1.04). CONCLUSION VBCQ has a higher eradication rate on Hp than PBCQ, while its adverse reactions and compliance are similar to PBCQ. However, we conservatively believe that in Hp eradication, the VBCQ is not inferior to PBCQ because of the small absolute difference.
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Affiliation(s)
- Yujie Cheng
- Department of Pharmacy, Xiangyang No. 1 People's Hospital, Hubei University of Medicine
| | - Lin Yang
- Department of Pharmacology, Medical College of Hubei University of Arts and Sciences
| | - Si Xu
- Department of Pharmacy, the Fourth Clinical College of Hubei University of Medicine
| | - Chong Zhang
- Department of Pharmacy, Xiangyang No. 1 People's Hospital, Hubei University of Medicine
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Scarpignato C, Hunt RH. Potassium-competitive Acid Blockers: Current Clinical Use and Future Developments. Curr Gastroenterol Rep 2024; 26:273-293. [PMID: 39145848 PMCID: PMC11401795 DOI: 10.1007/s11894-024-00939-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/09/2024] [Indexed: 08/16/2024]
Abstract
PURPOSE OF THE REVIEW Acid suppression with proton pump inhibitors (PPIs) represents the standard of care in the treatment of acid-related diseases. However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades. The aims of this review are to summarize the current status and future development of the new class of antisecretory drugs (potassium-competitive acid blockers, P-CABs) that have recently been introduced into medical practice. RECENT FINDINGS Over the past decades, clinical needs unmet by the current acid suppressants have been recognized, especially in the management of patients with GERD, Helicobacter pylori infection and NSAID-related peptic ulcer. The failure to address these needs is mainly due to their inability to achieve a consistent acid suppression in all patients and, particularly, to control nighttime acidity. It was then realized that an extended duration of acid suppression would exert additional benefits. The available data with P-CABs show that they are able to address these unmet clinical needs. Four different P-CABs (vonoprazan, tegoprazan, fexuprazan and keverprazan) are currently available. However, only two of them are approved outside Asia. Vonoprazan is available in North, Central and South America while tegoprazan is marketed only in Latin American countries. Two other compounds (namely linazapran glurate and zestaprazan) are presently under clinical development. While clinical trials on GERD have been performed with all P-CABs, only vonoprazan and tegoprazan have been investigated as components of Helicobacter pylori eradication regimens. The available data show that-in the above two clinical indications-P-CABs provide similar or better efficacy in comparison with PPIs. Their safety in the short-term overlaps that of PPIs, but data from long-term treatment are needed.
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Affiliation(s)
- Carmelo Scarpignato
- Department of Medicine & Surgery, University of Parma, Parma, Italy.
- Department of Health Sciences, United Campus of Malta, Msida, Malta.
- Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, Hong Kong.
- Faculty of Medicine, University of Nantes, Nantes, France.
| | - Richard H Hunt
- Department of Medicine, Division of Gastroenterology and Farncombe Family Digestive, Health Research Institute, McMaster University, Hamilton, ON, Canada
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Sakaguchi K, Naito T, Hoshikawa K, Miyadera Y, Tanaka H, Nakatsugawa E, Furuta T, Sugimoto K, Kawakami J. Characterization of plasma vonoprazan and CYP3A activity using its endogenous marker and genetic variants in patients with digestive system disorders. Drug Metab Pharmacokinet 2024; 58:101027. [PMID: 39428315 DOI: 10.1016/j.dmpk.2024.101027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 06/20/2024] [Accepted: 06/25/2024] [Indexed: 10/22/2024]
Abstract
Factors that determine clinical responses to vonoprazan remain unknown. This study aimed to characterize plasma vonoprazan and CYP3A activity using its endogenous marker and genetic variants in patients with digestive system disorders. Fifty-three patients who were receiving vonoprazan for at least 3 days were enrolled. Blood samples for determination of plasma vonoprazan and its metabolite (ODA-VP) were obtained. Plasma 4β-hydroxycholesterol (4β-OHC), CYP3A5 and ABCB1 genotypes, and plasma gastrin were determined. CYP3A recognition for vonoprazan was evaluated using recombinant CYP3A proteins. Plasma vonoprazan levels exhibited a large interindividual variation. The absolute plasma concentration of vonoprazan was correlated with its dose-normalized value, and had a positive correlation with the inverse value of its metabolic ratio. A negative correlation was observed between plasma vonoprazan and 4β-OHC levels. The metabolic ratio of vonoprazan was positively correlated with the plasma 4β-OHC level. Genetic variants of CYP3A5 and ABCB1 were not associated with the plasma concentration of vonoprazan and its metabolic ratio. Possible saturated metabolism of vonoprazan to its major metabolite was observed at a therapeutic dose. Although the CYP3A5 genotype did not alter plasma vonoprazan, CYP3A activity based on plasma 4β-OHC partially explained the variation in plasma vonoprazan in patients with digestive system disorders.
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Affiliation(s)
- Kenta Sakaguchi
- Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takafumi Naito
- Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Pharmacy, Shinshu University Hospital, Matsumoto, Nagano, Japan.
| | - Kohei Hoshikawa
- Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yukari Miyadera
- Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hironari Tanaka
- Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Emi Nakatsugawa
- Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takahisa Furuta
- First Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Ken Sugimoto
- First Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Junichi Kawakami
- Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan
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Setia A, Challa RR, Vallamkonda B, Vaishali, Viswanadh MK, Muthu MS. Clinical Implications of Proton Pump Inhibitors and Vonoprazan Micro/Nano Drug Delivery Systems for Gastric Acid-Related Disorders and Imaging. Nanotheranostics 2024; 8:535-560. [PMID: 39507107 PMCID: PMC11539181 DOI: 10.7150/ntno.100727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 09/17/2024] [Indexed: 11/08/2024] Open
Abstract
Excessive stomach acid or bacterial infection are the root causes of gastric acid-related disorders, such as peptic ulcer disease and gastroesophageal reflux disease. Proton pump inhibitors including lansoprazole, omeprazole, esomeprazole, rabeprazole, etc. are medications used to treat gastric acid-related diseases. One of the most effective drugs for treating gastroesophageal reflux disease is vonoprazan, owing to its ability to strongly inhibit gastric acid. Proton pump inhibitors and vonoprazan work in distinct ways to prevent the production of stomach acid. Vonoprazan inhibits acid secretion by blocking the potassium-competitive acid blocker receptor, whereas proton pump inhibitors function by irreversibly blocking the proton pump in the parietal cells of the stomach. Delayed release tablets, delayed release capsules, minitablets, pellets, bilayer, floating, mucoadhesive tablets and nanoparticles, are some of the methods used in the development of micro/nano formulations with proton pump inhibitors and vonoprazan. Diagnosis and therapy of gastric acid-related illnesses, particularly those treated with drugs such as vonoprazan and proton pump inhibitors, rely heavily on imaging modalities such as CT scans, X-rays, endoscopy, fluorescence and HRM imaging. This review provides a comprehensive update on various micro/nanoformulations of proton pump inhibitors and vonoprazan. Moreover, we provide an outlook on clinical imaging of proton pump inhibitors and vonoprazan formulation for gastric acid related diseases. We have limited our discussion to case studies and clinical trials on proton pump inhibitors and vonoprazan for gastric acid related disease.
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Affiliation(s)
- Aseem Setia
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi-221005, India
| | - Ranadheer Reddy Challa
- Department of Pharmaceutical Science, School of Applied Sciences and Humanities, VIGNAN's Foundation for Science, Technology & Research, Vadlamudi-522213, Andhra Pradesh, India
| | - Bhaskar Vallamkonda
- Department of Pharmaceutical Science, School of Applied Sciences and Humanities, VIGNAN's Foundation for Science, Technology & Research, Vadlamudi-522213, Andhra Pradesh, India
| | - Vaishali
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi-221005, India
| | - Matte Kasi Viswanadh
- Department of Pharmaceutics, KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Greenfields, Vaddeswaram 522302, AP, India
| | - Madaswamy S. Muthu
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi-221005, India
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25
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Geeratragool T, Kaosombatwattana U, Boonchote A, Chatthammanat S, Preechakawin N, Srichot J, Sudcharoen A, Sirisunhirun P, Termsinsuk P, Rugivarodom M, Limsrivilai J, Maneerattanaporn M, Pausawasdi N, Leelakusolvong S. Comparison of Vonoprazan Versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial. Gastroenterology 2024; 167:778-787.e3. [PMID: 38582271 DOI: 10.1053/j.gastro.2024.03.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 03/13/2024] [Accepted: 03/24/2024] [Indexed: 04/08/2024]
Abstract
BACKGROUND & AIMS High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aimed to compare the efficacy of vonoprazan vs PPI for preventing high-risk PU rebleeding after hemostasis. METHODS A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3- and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety. RESULTS Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference, -3.3; 95% confidence interval, -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P < .001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups. CONCLUSION In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).
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Affiliation(s)
- Tanawat Geeratragool
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
| | - Uayporn Kaosombatwattana
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand.
| | - Arpapun Boonchote
- Division of Medicine, School of Medicine, Vachira Phuket Hospital, Phuket, Thailand
| | | | | | - Jompol Srichot
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
| | - Asawin Sudcharoen
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Nakhon Nayok, Thailand
| | | | - Panotpol Termsinsuk
- Gastroenterology Unit, School of Medicine, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
| | - Manus Rugivarodom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
| | - Julajak Limsrivilai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
| | - Monthira Maneerattanaporn
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
| | - Nonthalee Pausawasdi
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
| | - Somchai Leelakusolvong
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
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Grosso R, Benito E, Carbajo-Gordillo AI, Díaz MJ, García-Martín MG, de-Paz MV. Advanced interpenetrating polymer networks for innovative gastroretentive formulations targeting Helicobacter pylori gastric colonization. Eur J Pharm Sci 2024; 200:106840. [PMID: 38909691 DOI: 10.1016/j.ejps.2024.106840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 04/25/2024] [Accepted: 06/20/2024] [Indexed: 06/25/2024]
Abstract
The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand for innovative therapeutic strategies. This study addresses this urgency through the development of tailored semi-interpenetrating polymer networks (semi-IPN) serving as gastroretentive matrices for amoxicillin (AMOX). They are biodegradable, absorb significant volume of simulated gastric fluid (swelling index > 360 %) and exhibit superporous microstructures, remarkable mucoadhesion, and buoyancy. The investigation includes assessment at pH 1.2 for comparative analysis with prior studies and, notably, at pH 5.0, reflecting the acidic environment in H. pylori-infected stomachs. The semi-IPN demonstrated gel-like structures, maintaining integrity throughout the 24-hour controlled release study, and disintegrating upon completing their intended function. Evaluated in gastroretentive drug delivery system performance, AMOX release at pH 1.2 and pH 5.0 over 24 h (10 %-100 %) employed experimental design methodology, elucidating dominant release mechanisms. Their mucoadhesive, buoyant, three-dimensional scaffold stability, and gastric biodegradability make them ideal for accommodating substantial AMOX quantities. Furthermore, exploring the inclusion of the potassium-competitive acid blocker (P-CAB) vonoprazan (VONO) in AMOX-loaded formulations shows promise for precise and effective drug delivery. This innovative approach has the potential to combat H. pylori infections, thereby preventing the gastric cancer induced by this pathogen.
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Affiliation(s)
- Roberto Grosso
- Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Prof. García González, n. 2, 41012, Seville, Spain
| | - Elena Benito
- Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Prof. García González, n. 2, 41012, Seville, Spain.
| | - Ana I Carbajo-Gordillo
- Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Prof. García González, n. 2, 41012, Seville, Spain
| | | | - M Gracia García-Martín
- Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Prof. García González, n. 2, 41012, Seville, Spain
| | - M-Violante de-Paz
- Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Prof. García González, n. 2, 41012, Seville, Spain.
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Kim Y, Bae S, Chung WK, Kwon J, Song I, Lee S. Exploration of pharmacokinetic differences between East Asians and Caucasians: insights from pharmacokinetic studies in healthy subjects. Transl Clin Pharmacol 2024; 32:127-136. [PMID: 39386270 PMCID: PMC11458340 DOI: 10.12793/tcp.2024.32.e15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 09/10/2024] [Accepted: 09/20/2024] [Indexed: 10/12/2024] Open
Abstract
Interethnic differences in the pharmacokinetics of drugs result from a complex interplay of environmental, genetic, and demographic factors. Identifying ethnic differences in pharmacokinetics is challenging due to the multifaceted contributions of the underlying factors. To address these challenges, this paper reviews 9 pharmacokinetic studies meeting the following criteria: (A) Conducted at Seoul National University Hospital from 2013 to 2022 as a single-center study. (B) Pharmacokinetic studies involving both East Asians (Korean, Japanese, or Chinese) and Caucasians. (C) Study drugs were administered orally. (D) Raw data was provided for reanalysis. This retrospective analysis aimed to investigate the existence of ethnic differences in drug exposure and understand the possible factors contributing to these variabilities. Pharmacokinetic, demographic, and clinical laboratory test data were analyzed to assess potential pharmacokinetic differences between East Asians and Caucasians. This assessment involved calculating the geometric mean ratio of dose-normalized area under the time-concentration curve (AUC) and dose- and weight-normalized AUC, along with their 90% confidence intervals. Additionally, pharmacological information, including metabolic pathways, was gathered from the investigational brochure or the respective country's drug label. Among 9 studies, 4 studies demonstrated approximately 1.3 to 1.8 times higher drug exposure in East Asians compared to Caucasians. These drugs were primarily eliminated through hepatic metabolism, with less than 5% excreted unchanged in the urine. Two drugs were metabolized by hepatic cytochrome P450 3A4, one by glutathione S-transferase, and specific metabolic pathways for another drug were not identified. Further research is needed to assess the causes of ethnic variability in these drugs.
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Affiliation(s)
- Yoonjin Kim
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Seoul National University Hospital, Seoul 03080, Korea
| | - Sungyeun Bae
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Seoul National University Hospital, Seoul 03080, Korea
| | - Woo Kyung Chung
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Seoul National University Hospital, Seoul 03080, Korea
| | - Jihoon Kwon
- Department of Statistics, APACE, Seoul 04619, Korea
| | - Ildae Song
- Department of Pharmaceutical Science and Technology, Kyungsung University, Busan 48434, Korea
| | - SeungHwan Lee
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Seoul National University Hospital, Seoul 03080, Korea
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Al-Frejat Z, Martini N, Esper A, Al-Frejat D, Younes S, Hanna M. GERD: Latest update on acid-suppressant drugs. CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2024; 7:100198. [PMID: 39282236 PMCID: PMC11393603 DOI: 10.1016/j.crphar.2024.100198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 08/07/2024] [Accepted: 08/19/2024] [Indexed: 09/18/2024] Open
Abstract
GERD is a very familiar diagnosis among health care providers due to its massive spread, and its symptoms can affect the quality of life for a respectable slice of its patients. Therefore, what can only be described as a logical consequence, a pursuit of a treatment that can both relieve symptoms and have minimal side effects is still ongoing to cover the large demographic affected by GERD. In the following review, analysis will be made of GERD, including possible regulatory activity, of certain drugs to the already discussed pathways involved in GERD patients.
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Affiliation(s)
- Zyad Al-Frejat
- Faculty of Medicine, Al Baath University, Homs, Syria
- Faculty of Medicine, Damascus University, Damascus, Syria
| | - Nafiza Martini
- Faculty of Medicine, Damascus University, Damascus, Syria
- Stemosis for Scientific Research, Damascus, Syria
| | - Alia Esper
- Faculty of Medicine, Al Baath University, Homs, Syria
- Stemosis for Scientific Research, Damascus, Syria
| | - Diana Al-Frejat
- Faculty of Medicine, Damascus University, Damascus, Syria
- Faculty of Dentistry, Syrian Private University, Damascus, Syria
| | - Samer Younes
- Faculty of Pharmacy, Tartous University, Tartous, Syria
- Stemosis for Scientific Research, Damascus, Syria
| | - Majd Hanna
- Faculty of Medicine, Damascus University, Damascus, Syria
- Stemosis for Scientific Research, Damascus, Syria
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Chiu YT, Lee FJ, Kuo CY, Chen YT, Lin YC, Liang KS, Wu CY, Lin RT, Lin JT, Chang CY. Seven-Day Vonoprazan-Based Triple Therapy as First-Line Helicobacter pylori Treatment in Comparison With Extended Sequential Therapy: A Randomized Controlled Trial. Helicobacter 2024; 29:e13129. [PMID: 39164808 DOI: 10.1111/hel.13129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 07/24/2024] [Accepted: 08/04/2024] [Indexed: 08/22/2024]
Abstract
BACKGROUND Vonoprazan, a potassium-competitive acid blocker, has demonstrated greater potency and a longer duration of acid suppression when compared to the proton pump inhibitors. However, data regarding the comparison between vonoprazan-based triple therapy with standard treatment for first-line Helicobacter pylori treatment are limited. This study aimed to compare the efficacy between 7-day vonoprazan-based triple therapy with high-dose amoxicillin (VAC-7) and 14-day extended sequential therapy (S-14). MATERIALS AND METHODS This was a single-center prospective randomized controlled trial following a noninferiority design. Subjects over 20 years old with confirmed H. pylori infection were enrolled prospectively from Fu Jen Catholic University Hospital. They were randomly assigned to the VAC-7 or S-14 group. The primary endpoint was the eradication rate in first-line treatment, evaluated by urea breath test, with noninferiority determined using the Farrington-Manning method. The secondary outcome included adverse effect rates and compliance, assessed through self-administered questionnaires. RESULTS Between December 2021 and June 2023, a total of 628 patients were recruited. The eradication rates by per-protocol analysis and intention-to-treat analysis were 88.6%/81.8% for VAC-7 and 90.3%/81.4% for S-14, respectively. The VAC-7 was non-inferior to S-14 in terms of ITT analysis. Subjects experienced fewer incidences of nausea, anorexia, dizziness, fatigue, and any severe adverse events in the VAC-7 group. Compliance was higher in the VAC-7 group, with 94% taking all the pills correctly. CONCLUSIONS Our findings supported the use of 7-day vonoprazan triple therapy with high-dose amoxicillin as the standard first-line treatment for H. pylori infection. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT05371249.
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Affiliation(s)
- Yu-Tse Chiu
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei, Taiwan
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
| | - Fu-Jen Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei, Taiwan
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
| | - Chen-Ya Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei, Taiwan
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
| | - Yu-Tsung Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei, Taiwan
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
| | - Yang-Chao Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei, Taiwan
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
| | - Kai-Shun Liang
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei, Taiwan
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
| | - Chun-Ying Wu
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan
- College of Public Health, China Medical University, Taichung, Taiwan
| | - Ro-Ting Lin
- Department of Occupational Safety and Health, College of Public Health, China Medical University, Taichung, Taiwan
| | - Jaw-Town Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei, Taiwan
- Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan
| | - Chi-Yang Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei, Taiwan
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
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Ding YM, Duan M, Han ZX, Song XH, Zhang FL, Wang Z, Ning Z, Zeng SY, Kong QZ, Zhang WL, Liu J, Wan M, Lin MJ, Lin BS, Nan XP, Wang H, Li YY, Zuo XL, Li YQ. Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days. Dig Dis Sci 2024; 69:2540-2547. [PMID: 38700630 DOI: 10.1007/s10620-024-08460-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 04/20/2024] [Indexed: 07/19/2024]
Abstract
BACKGROUND Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).
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Affiliation(s)
- Yu-Ming Ding
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Miao Duan
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Zhong-Xue Han
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Xiao-Hui Song
- The People's Hospital of Jimo., Qingdao, Shandong, China
| | - Feng-Lan Zhang
- Heze Municipal 3rd People's Hospital, Heze, Shandong, China
| | - Zhi Wang
- Maternity and Child Care Health Center of Dezhou, Dezhou, Shandong, China
| | - Zhang Ning
- PKUCare Luzhong Hospital, Zibo, Shandong, China
| | - Shu-Yan Zeng
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Qing-Zhou Kong
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Wen-Lin Zhang
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Jing Liu
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Meng Wan
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Min-Juan Lin
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Bo-Shen Lin
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Xue-Ping Nan
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Hui Wang
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Yue-Yue Li
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China.
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China.
| | - Xiu-Li Zuo
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Yan-Qing Li
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
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Pattarapuntakul T, Wong T, Wetwittayakhlang P, Netinatsunton N, Keeratichananont S, Kaewdech A, Jandee S, Chamroonkul N, Sripongpun P, Lakatos PL. Efficacy of Vonoprazan vs. Intravenous Proton Pump Inhibitor in Prevention of Re-Bleeding of High-Risk Peptic Ulcers: A Randomized Controlled Pilot Study. J Clin Med 2024; 13:3606. [PMID: 38930134 PMCID: PMC11204564 DOI: 10.3390/jcm13123606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 06/03/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024] Open
Abstract
Background: Proton pump inhibitor (PPI) therapy is well-established for its effectiveness in reducing re-bleeding in high-risk peptic ulcer patients following endoscopic hemostasis. Vonoprazan (VPZ) has demonstrated the capacity to achieve gastric pH levels exceeding 4, comparable to PPIs. This study aims to evaluate the comparative efficacy of intravenous PPI infusion versus VPZ in preventing re-bleeding after endoscopic hemostasis in patients with high-risk peptic ulcers. Methods: A randomized, double-blind, controlled, and double-dummy design was employed. Patients with peptic ulcer bleeding (Forrest class IA/IB or IIA/IIB) who underwent endoscopic hemostasis were randomly assigned to either the PPI group or the VPZ group. Re-bleeding rates at 3, 7, and 30 days, the number of blood transfusions required, length of hospitalization, and ulcer healing rate at 56 days were assessed. Results: A total of 44 eligible patients were enrolled, including 20 patients (PPI group, n = 11; VPZ group, n = 9) with high-risk peptic ulcers. The mean age was 66 years, with 70% being male. Re-bleeding within 72 h occurred in 9.1% of the PPI group versus 0% in the VPZ group (p = 1.000). There was no significant difference in re-bleeding rates within 7 days and 30 days (18.2% vs. 11.1%, p = 1.000). Additionally, the ulcer healing rate did not significantly differ between the groups (87.5% vs. 77.8%). Conclusions: This pilot study demonstrates comparable efficacy between oral vonoprazan and continuous PPI infusion in preventing recurrent bleeding events among high-risk peptic ulcer patients following successful endoscopic hemostasis.
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Affiliation(s)
- Tanawat Pattarapuntakul
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
| | - Thanawin Wong
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
| | - Panu Wetwittayakhlang
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Nisa Netinatsunton
- Nanthana-Kriangkrai Chotiwattanaphan (NKC) Institute of Gastroenterology and Hepatology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (N.N.); (S.K.)
| | - Suriya Keeratichananont
- Nanthana-Kriangkrai Chotiwattanaphan (NKC) Institute of Gastroenterology and Hepatology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (N.N.); (S.K.)
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
| | - Sawangpong Jandee
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
| | - Naichaya Chamroonkul
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
| | - Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
| | - Peter L. Lakatos
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
- Department of Internal Medicine and Oncology, Semmelweis University, 1085 Budapest, Hungary
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Chen X, Chen T, Huang Y, Wang M, Wang Y, Wu P, Xia X, Du P, Wu J, Shen J, Jia Y. LC-MS/MS method for quick detection of vonoprazan fumarate in human plasma: Development, validation and its application to a bioequivalence study. Biomed Chromatogr 2024; 38:e5860. [PMID: 38558021 DOI: 10.1002/bmc.5860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 02/03/2024] [Accepted: 02/21/2024] [Indexed: 04/04/2024]
Abstract
A liquid chromatography-tandem mass spectrometry method with vonoprazan fumarate-d4 as a stable isotope-labeled internal standard was developed and validated aiming at quantification of vonoprazan fumarate in human plasma for a bioequivalence study. Chromatographic separation was achieved by acetonitrile one-step protein precipitation using a gradient elution of 0.1% formic acid aqueous solution and acetonitrile with a run time of 3.65 min. Detection was carried out on a tandem mass spectrometer in multiple reaction monitoring mode via a positive electrospray ionization interface. The multiple reaction monitoring mode of precursor-product ion transitions for vonoprazan fumarate and vonoprazan fumarate-d4 were m/z 346.0 → 315.1 and 350.0 → 316.0, respectively. The linear range was 0.150-60.000 ng/ml. This method was fully validated with acceptable results in terms of selectivity, carryover, lower limit of quantification, calibration curve, accuracy, precision, dilution effect, matrix effect, stability, recovery and incurred sample reanalysis. A successful application of this method was realized in the bioequivalence study of vonoprazan fumarate tablet (20 mg) among healthy Chinese volunteers.
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Affiliation(s)
- Xinyan Chen
- Anhui Provincial Center of Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People's Republic of China
- School of pharmacy, Wannan Medical College, Wuhu, Anhui, People's Republic of China
| | - Tao Chen
- Jiangsu Wangao Pharmaceutical Co., Ltd., Nantong, Jiangsu, People's Republic of China
| | - Yunzhe Huang
- School of pharmacy, Wannan Medical College, Wuhu, Anhui, People's Republic of China
| | - Minhui Wang
- Anhui Provincial Center of Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People's Republic of China
| | - Yaqin Wang
- Anhui Provincial Center of Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People's Republic of China
| | - Ping Wu
- Anhui Provincial Center of Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People's Republic of China
| | - Xiaocui Xia
- Anhui Provincial Center of Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People's Republic of China
| | - Pengfei Du
- School of pharmacy, Wannan Medical College, Wuhu, Anhui, People's Republic of China
| | - Jianbang Wu
- School of pharmacy, Wannan Medical College, Wuhu, Anhui, People's Republic of China
| | - Jie Shen
- Anhui Provincial Center of Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People's Republic of China
- School of pharmacy, Wannan Medical College, Wuhu, Anhui, People's Republic of China
| | - Yuanwei Jia
- Anhui Provincial Center of Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People's Republic of China
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Simadibrata DM, Lesmana E, Fass R. Vonoprazan is superior to lansoprazole for healing of severe but not mild erosive esophagitis: A systematic review with meta-analysis of randomized controlled trials. J Gastroenterol Hepatol 2024; 39:988-999. [PMID: 38353152 DOI: 10.1111/jgh.16486] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 12/12/2023] [Accepted: 12/27/2023] [Indexed: 06/19/2024]
Abstract
BACKGROUND AND AIM Healing rates of severe erosive esophagitis (EE; Los Angeles [LA] Grade C/D) in patients treated with a proton pump inhibitor (PPI) is suboptimal (~60-70%). Vonoprazan, a potassium-competitive acid blocker, is suggested to have better healing rates in patients with severe EE. This meta-analysis compares the efficacy and safety of vonoprazan 20 mg versus lansoprazole 30 mg daily in healing EE, specifically in those with LA Grade C/D. METHODS We searched MEDLINE, Embase, and CENTRAL on May 24, 2023. Studies that randomized EE patients to vonoprazan 20 mg daily or lansoprazole 30 mg daily and compared healing rates were included. The risk of bias was assessed using Cochrane's Risk of Bias 2 tool. The fixed-effect model was used to obtain the pooled efficacy and safety outcomes. Subgroup analysis was done to compare healing rates in mild (LA Grade A/B) versus severe EE and based on study location. RESULTS Four randomized controlled trials (RCTs) with low risks of bias comprising 2208 participants were included. Vonoprazan 20 mg was superior to lansoprazole 30 mg daily in healing severe EE at all weeks (Week 2 RR 1.294 [95% CI 1.169-1.433], Week 4 1.160 [1.059-1.270], and Week 8 1.175 [95% CI 1.107-1.247]), but was similar for mild EE at all weeks (P-interaction < 0.01). Vonoprazan 20 mg was more efficacious than lansoprazole 30 mg at Week 8 in Western versus Asian studies (P-interaction < 0.01). Any, serious, and drug-related treatment-emergent adverse events were comparable between groups. CONCLUSION Vonoprazan 20 mg is superior to lansoprazole 30 mg for healing severe EE but not mild EE. Vonoprazan 20 mg daily has a similar safety profile to lansoprazole 30 mg daily.
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Affiliation(s)
- Daniel Martin Simadibrata
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Elvira Lesmana
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
- Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, MetroHealth Medical System, Case Western Reserve University, Cleveland, Ohio, USA
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Fossmark R, Olaisen M. Changes in the Gastrointestinal Microbiota Induced by Proton Pump Inhibitors-A Review of Findings from Experimental Trials. Microorganisms 2024; 12:1110. [PMID: 38930492 PMCID: PMC11205704 DOI: 10.3390/microorganisms12061110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 05/21/2024] [Accepted: 05/27/2024] [Indexed: 06/28/2024] Open
Abstract
The use of proton pump inhibitors (PPIs) has increased considerably in many Western countries, and there is concern that numerous conditions and diseases associated with PPI use may be adverse events. The main function of gastric acid is to defend the organism against orally ingested microorganisms, and there is also concern that alterations not only in the gastric microbiome but also the downstream intestinal microbiome may increase the risk of disease or alter the course of preexisting disease. The current study is a systematic review of the available evidence from experimental trials investigating the effects of PPIs on the gastrointestinal microbiota by next-generation sequencing. Thirteen studies were identified. The effects of PPIs were seen on alterations in diversity and richness in some of the studies, while a larger proportion of the studies detected alterations at various taxonomic levels. The general finding was that PPI use caused an increase in bacteria normally found in the oral microbiota in both the upper and lower GI tract. The most consistent taxonomic alterations seemed to be increases in oral flora along the axis Streptococcaceae and Streptococcus at genus level and various Streptococcus spp., as well as Veillonellaceae, Veillonella and Haemophilus.
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Affiliation(s)
- Reidar Fossmark
- Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway;
- Centre for Obesity Research, Clinic of Surgery, St. Olav’s University Hospital, 7030 Trondheim, Norway
- Medicus Endoscopy, 7042 Trondheim, Norway
| | - Maya Olaisen
- Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway;
- Department of Gastroenterology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
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Jiang Y, Zhang R, Fang Y, Zhao R, Fu Y, Ren P, Zhan Q, Shao M. P-CAB versus PPI in the eradication of Helicobacter pylori: a systematic review and network meta-analysis. Therap Adv Gastroenterol 2024; 17:17562848241241223. [PMID: 38751605 PMCID: PMC11095192 DOI: 10.1177/17562848241241223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 03/06/2024] [Indexed: 05/18/2024] Open
Abstract
Background The efficacy and safety of potassium-competitive acid blockers (P-CABs) in the eradication of Helicobacter pylori (Hp) remains controversial when compared with proton pump inhibitors (PPIs). Objectives The current study set out to compare the differences in the eradication rate and adverse reactions between eradication regimens based on P-CAB or PPI drugs and the differences between the vonoprazan-based and the tegoprazan-based regimens to explore the efficacy and safety of different Hp eradication regimens. Data sources and methods Databases including PubMed, EMBASE, Cochrane Library, and WOS were searched from the inception of these databases up to July 2023, and eligible randomized controlled trials (RCTs) were included. The outcome measures were the eradication rate and the incidence of adverse reactions of different regimens in treating Hp. The results were estimated as relative risk (RR) and its 95% confidence interval (CI), and R 4.2.1 software was used to perform the network meta-analysis (NMA). Results A total of 20 studies were included in the analysis, involving 5815 patients with Hp. In terms of eradication rate, the 2-week vonoprazan-based triple regimen (V-Tri-2w) was the best, which was superior to the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 0.9, 95% CI: (0.85-0.95)] and the 1-week tegoprazan-based triple regimen [T-Tri-1w, RR = 0.79, 95% CI: (0.64-0.97)]; the 2-week tegoprazan-based quadruple regimen (T-Qua-2w) was superior to the 1-week PPI-based triple regimen [P-Tri-1w, RR = 0.82, 95% CI: (0.67-0.99)], and there was no difference between the remaining tegoprazan-based regimens and the PPI-based or vonoprazan-based regimens. In terms of the incidence of adverse reactions, the 2-week vonoprazan-based binary regimen (V-Bi-2w) was lower than that of the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 1.98, 95% CI: (1.57-2.52)]; there was no significant difference between 1 and 2 weeks for each regimen, such as the vonoprazan-based triple regimen [RR = 1.11, 95% CI: (0.82-1.52)]. Conclusion In the eradication treatment of Hp, the efficacy and safety of vonoprazan-based regimens are generally better than those of PPI-based regimens. Among them, the V-Tri-2w regimen has the highest eradication rate and may be the preferred choice for Hp eradication.
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Affiliation(s)
- Yutong Jiang
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
- The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China
| | - Rongrong Zhang
- The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China
| | - Yuxuan Fang
- The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China
| | - Ruixia Zhao
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Yu Fu
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Pingping Ren
- The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China
| | - Qingqing Zhan
- The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China
| | - Mingyi Shao
- The First Affiliated Hospital of Henan University of Chinese Medicine, 19 Renmin Road, Jinshui District, Zhengzhou, Henan 450000, China
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Elsabaawy M, Shaban A, Al-Arab AE, Elbahr O, Edrees A, Afify S. Vonoprazan a novel potassium competitive acid blocker; another leap forward. PRZEGLAD GASTROENTEROLOGICZNY 2024; 19:135-142. [PMID: 38939071 PMCID: PMC11200074 DOI: 10.5114/pg.2024.139426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Accepted: 02/10/2023] [Indexed: 06/29/2024]
Abstract
INTRODUCTION The eradication rate of Helicobacter pylori (H. pylori) has decreased due to antibiotics resistance and inadequate acid suppression. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB), which has a rapid and sustained acid inhibitory effect and may be more effective than conventional proton pump inhibitors (PPIs) in H. pylori eradication. AIM to study the efficacy and safety of vonoprazan as a component of first-line H. pylori eradication treatment compared with conventional PPI-based therapy. MATERIAL AND METHODS This randomised (one to one) non-blinded study was conducted on 400 consecutive proven H. pylori infected patients, of whom 200 received vonoprazan-based triple therapy, while 200 patients received PPI-based triple therapy for 14 days. The study outcomes were evaluated as eradication rate and adverse events in both patient groups. RESULTS The eradication rate was 86% in the vonoprazan group and 74.5% in the PPI group. The vonoprazan eradication rate was significantly higher than that of PPIs (p = 0.004). There was no significant difference regarding adverse events between both patient groups. CONCLUSIONS Vonoprazan-based therapy was more effective than PPI-based therapy as a first-line H. pylori eradication treatment. Vonoprazan was generally safe and well tolerated.
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Affiliation(s)
- Maha Elsabaawy
- Depatment of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koum, Menoufia, Egypt
| | - Ahmed Shaban
- Depatment of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koum, Menoufia, Egypt
| | - Ahmed Ezz Al-Arab
- Depatment of internal Medicine, Faculty of Medicine, Menoufia University, Shebeen El-Koum, Menoufia, Egypt
| | - Osama Elbahr
- Depatment of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koum, Menoufia, Egypt
| | - Ahmed Edrees
- Depatment of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koum, Menoufia, Egypt
| | - Sameh Afify
- Depatment of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koum, Menoufia, Egypt
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Kim BW, Park JJ, Moon HS, Lee WS, Shim KN, Baik GH, Lim YJ, Lee HL, Youn YH, Park JC, Sung IK, Chung H, Moon JS, Kim GH, Hong SJ, Choi HS. The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study. Gut Liver 2024; 18:257-264. [PMID: 38384180 PMCID: PMC10938149 DOI: 10.5009/gnl230242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 08/18/2023] [Accepted: 08/22/2023] [Indexed: 02/23/2024] Open
Abstract
BACKGROUND/AIMS : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. METHODS : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. RESULTS : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. CONCLUSIONS : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.
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Affiliation(s)
- Byung-Wook Kim
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jong Jae Park
- Division of Gastroenterology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Hee Seok Moon
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
| | - Wan Sik Lee
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea
| | - Ki-Nam Shim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Gwang Ho Baik
- Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
| | - Yun Jeong Lim
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Hang Lak Lee
- Department of Internal Medicine, Hanyang University Medical Center, Seoul, Korea
| | - Young Hoon Youn
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Chul Park
- Department of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - In-Kyung Sung
- Department of Internal Medicine, Konkuk University Medical Center, Konkuk University College of Medicine, Seoul, Korea
| | - Hyunsoo Chung
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Seop Moon
- Department of Internal Medicine, Inje University Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University College of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Su Jin Hong
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Hyuk Soon Choi
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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Liu Z, Chen X, Sun DJ, Zhao WW, Kou L, Zheng WW, Hao JR, Gao FY. Comparison of vonoprazan-based dual therapy with vonoprazan-based bismuth quadruple therapy for treatment-naive patients with Helicobacter pylori infection: A propensity score matching analysis. Medicine (Baltimore) 2024; 103:e37476. [PMID: 38457567 PMCID: PMC10919513 DOI: 10.1097/md.0000000000037476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 02/07/2024] [Accepted: 02/12/2024] [Indexed: 03/10/2024] Open
Abstract
Vonoprazan, a novel acid suppressant and the first potassium-competitive acid blocker, has the potential to enhance the eradication rate of Helicobacter pylori due to its robust acid-suppressing capacity. This study aimed to compare the efficacy of vonoprazan-based dual therapy (vonoprazan-amoxicillin, VA) with vonoprazan-based bismuth quadruple therapy (VBQT) as a first-line treatment for H pylori infection. This retrospective single-center non-inferiority study was conducted in China. Treatment-naive H pylori-positive patients aged 18 to 80 received one of the 2 treatment regimens at our center. The VA group received vonoprazan 20 mg twice daily and amoxicillin 1000 mg 3 times daily for 14 days, whereas the VBQT group received vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg twice daily for 14 days. The eradication rate was evaluated 4 to 6 weeks after treatment using the carbon-13/14 urea breath test. Propensity score matching was used to analyze eradication rates, adverse events (AEs), and patient compliance between the 2 groups. Initially, 501 patients were included, and after propensity score analysis, 156 patients were selected for the study. Intention-to-treat analysis showed eradication rates of 87.2% (95% CI, 79.8-94.6%) for the VA group and 79.5% (95% CI, 70.5-88.4%) for the VBQT group (P = .195). Per-protocol analysis demonstrated rates of 94.4% (95% CI, 89.2-99.7%) for the VA group and 96.8% (95% CI, 92.4-100%) for the VBQT group (P = .507). Non-inferiority was confirmed between the 2 groups, with P values < .025. The VA group showed a lower rate of AEs (10.3% vs 17.9%, P = .250) compared to the VBQT group. There were no significant differences in patient compliance between the 2 groups. In treatment-naive patients with H pylori infection, both the 14-day VA and VBQT regimens demonstrated comparable efficacy, with excellent eradication rates. Moreover, due to reduced antibiotic usage, lower rate of AEs, and lower costs, VA dual therapy should be prioritized.
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Affiliation(s)
- Zhu Liu
- Department of Gastroenterology, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China
| | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Dong-Jie Sun
- Department of Digestive Diseases, The Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China
| | - Wen-Wen Zhao
- Department of Gastroenterology, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China
| | - Luan Kou
- Department of Gastroenterology, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China
| | - Wen-Wen Zheng
- Department of Gastroenterology, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China
| | - Jiao-Rong Hao
- Department of Gastroenterology, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China
| | - Feng-Yu Gao
- Department of Gastroenterology, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China
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Shirley M. Vonoprazan: A Review in Helicobacter pylori Infection. Drugs 2024; 84:319-327. [PMID: 38388872 PMCID: PMC11090951 DOI: 10.1007/s40265-023-01991-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2023] [Indexed: 02/24/2024]
Abstract
Treatment for the eradication of Helicobacter pylori infection, a leading cause of peptic ulcer disease and an important risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma, is indicated whenever infection is identified. However, treatment success rates with current guideline-recommended proton-pump inhibitor (PPI)-based regimens remain suboptimal, with one potential factor associated with treatment failure being inadequate acid suppression. Vonoprazan (Voquezna®) is a first-in-class potassium-competitive acid blocker with the potential to provide potent and sustained acid suppression. Following clinical trials conducted mainly in Asia (supported by post-marketing experience from Asia) and the phase III PHALCON-HP trial conducted in the USA and Europe, vonoprazan is now approved in the USA for use in combination with amoxicillin (dual therapy) or amoxicillin and clarithromycin (triple therapy) for the treatment of H. pylori infection in adults. The vonoprazan-based dual and triple therapy regimens were generally well tolerated in PHALCON-HP. In addition, vonoprazan has advantages including a rapid onset of action and no food effect, making vonoprazan-based dual and triple therapy regimens valuable alternatives to standard PPI-based triple therapy in the treatment of H. pylori infection.
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Affiliation(s)
- Matt Shirley
- Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
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40
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Antequera CM, Orleck K, Jacob R, Kenneally A, Wright WL. Potassium-competitive acid blockers: rethinking acid suppression for gastroesophageal reflux disease and Helicobacter pylori. Postgrad Med 2024; 136:131-140. [PMID: 38385191 DOI: 10.1080/00325481.2024.2320081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 02/13/2024] [Indexed: 02/23/2024]
Abstract
Gastroesophageal reflux disease (GERD) and Helicobacter pylori (H. pylori) infection are different disease states that are united by the core role of acid suppression in their management. In GERD, proton pump inhibitors (PPIs) have long been standard therapy based on abundant positive clinical trial data supporting their efficacy and safety. In H. pylori, PPIs are also a critical element of therapy in combination with 1 or more antibiotics to achieve and maintain a pH that maximizes the efficacy of therapy. Despite the considerable clinical success and widespread use of PPIs, room remains for agents with differentiated pharmacokinetic and pharmacodynamic profiles. The potassium-competitive acid blockers (PCABs) are mechanistically distinct from PPIs but are acid-stable and do not require activation of the proton pump by coadministration of food. In pharmacodynamic studies, these agents have shown greater durations of acid suppression above the critical threshold of pH 4 (for GERD) and pH 6 (for H. pylori), which have been shown to optimize therapeutic efficacy in these settings. These results have translated in clinical studies to similar and, in some cases, improved outcomes relative to PPIs in these disease states. This review summarizes current knowledge on the physiology of acid secretion, pathophysiology and management of GERD and H. pylori, and key characteristics and clinical trial data for PPIs and PCABs.
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Affiliation(s)
| | | | - Rinu Jacob
- Phathom Pharmaceuticals, Florham Park, NJ, USA
| | | | - Wendy L Wright
- Wright & Associates Family Healthcare PLLC, Amherst, NH, USA
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Wu K, Li X, Zhou Z, Zhao Y, Su M, Cheng Z, Wu X, Huang Z, Jin X, Li J, Zhang M, Liu J, Liu B. Predicting pharmacodynamic effects through early drug discovery with artificial intelligence-physiologically based pharmacokinetic (AI-PBPK) modelling. Front Pharmacol 2024; 15:1330855. [PMID: 38434709 PMCID: PMC10904617 DOI: 10.3389/fphar.2024.1330855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 02/02/2024] [Indexed: 03/05/2024] Open
Abstract
A mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model links the concentration-time profile of a drug with its therapeutic effects based on the underlying biological or physiological processes. Clinical endpoints play a pivotal role in drug development. Despite the substantial time and effort invested in screening drugs for favourable pharmacokinetic (PK) properties, they may not consistently yield optimal clinical outcomes. Furthermore, in the virtual compound screening phase, researchers cannot observe clinical outcomes in humans directly. These uncertainties prolong the process of drug development. As incorporation of Artificial Intelligence (AI) into the physiologically based pharmacokinetic/pharmacodynamic (PBPK) model can assist in forecasting pharmacodynamic (PD) effects within the human body, we introduce a methodology for utilizing the AI-PBPK platform to predict the PK and PD outcomes of target compounds in the early drug discovery stage. In this integrated platform, machine learning is used to predict the parameters for the model, and the mechanism-based PD model is used to predict the PD outcome through the PK results. This platform enables researchers to align the PK profile of a drug with desired PD effects at the early drug discovery stage. Case studies are presented to assess and compare five potassium-competitive acid blocker (P-CAB) compounds, after calibration and verification using vonoprazan and revaprazan.
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Affiliation(s)
- Keheng Wu
- Yinghan Pharmaceutical Technology (Shanghai) Co., Ltd., Shanghai, China
| | - Xue Li
- Yinghan Pharmaceutical Technology (Shanghai) Co., Ltd., Shanghai, China
| | - Zhou Zhou
- Yinghan Pharmaceutical Technology (Shanghai) Co., Ltd., Shanghai, China
| | - Youni Zhao
- Yinghan Pharmaceutical Technology (Shanghai) Co., Ltd., Shanghai, China
| | - Mei Su
- Jiangsu Carephar Pharmaceutical Co., Ltd., Nanjing, China
| | - Zhuo Cheng
- Yinghan Pharmaceutical Technology (Shanghai) Co., Ltd., Shanghai, China
| | - Xinyi Wu
- Yinghan Pharmaceutical Technology (Shanghai) Co., Ltd., Shanghai, China
| | - Zhijun Huang
- Yinghan Pharmaceutical Technology (Shanghai) Co., Ltd., Shanghai, China
| | - Xiong Jin
- School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, China
| | - Jingxi Li
- School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, China
| | - Mengjun Zhang
- School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, China
| | - Jack Liu
- Yinghan Pharmaceutical Technology (Shanghai) Co., Ltd., Shanghai, China
| | - Bo Liu
- School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, China
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Okubo K, Kudo T, Yoshihara S, Nakabayashi Y, Nakauchi K, Tanaka A, Saito M, Tsujisawa A, Goda H, Yamagishi Y, Otake C, Makino K, Takahashi H, Ito K. Physiologically based pharmacokinetic model analysis of the inhibitory effect of vonoprazan on the metabolic activation of proguanil. Drug Metab Pharmacokinet 2024; 54:100537. [PMID: 38086197 DOI: 10.1016/j.dmpk.2023.100537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 09/15/2023] [Accepted: 10/30/2023] [Indexed: 02/06/2024]
Abstract
We previously reported that repeated oral administration of vonoprazan (VPZ) followed by oral administration of proguanil (PG) in healthy adults increased blood concentration of PG and decreased blood concentration of its metabolite cycloguanil (CG) compared with administration of PG alone. In this study, we investigated whether this interaction can be quantitatively explained by VPZ inhibition of PG metabolism. In an in vitro study using human liver microsomes, VPZ inhibited CG formation from PG in a concentration-dependent manner, and the inhibition was enhanced depending on preincubation time. Then, a physiologically based pharmacokinetic (PBPK) model analysis was performed incorporating the obtained inhibition parameters. By fitting the blood concentration profiles of VPZ and PG/CG after VPZ and PG were orally administered alone to our PBPK model, parameters were obtained which can reproduce their concentration profiles. In contrast, when the VPZ inhibition parameters for CG formation from the in vitro study were incorporated, the predicted blood PG and CG concentrations were unchanged; the apparent dissociation constant had to be set to about 1/23 of the obtained in vitro value to reproduce the observed interaction. Further comprehensive evaluation is required, including the possibility that mechanisms other than metabolic inhibition may be involved.
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Affiliation(s)
- Kenjiro Okubo
- Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan
| | - Toshiyuki Kudo
- Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan; Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan.
| | - Sae Yoshihara
- Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan
| | - Yu Nakabayashi
- Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan
| | - Kana Nakauchi
- Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan
| | - Akimi Tanaka
- Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan
| | - Moe Saito
- Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan
| | - Ayumi Tsujisawa
- Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan
| | - Hitomi Goda
- Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan
| | - Yoshiaki Yamagishi
- Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan; Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan.
| | - Chinatsu Otake
- Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba, 278-8510, Japan
| | - Kosho Makino
- Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba, 278-8510, Japan.
| | - Hideyo Takahashi
- Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba, 278-8510, Japan.
| | - Kiyomi Ito
- Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan; Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan.
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Moss SF, Shah SC, Tan MC, El-Serag HB. Evolving Concepts in Helicobacter pylori Management. Gastroenterology 2024; 166:267-283. [PMID: 37806461 PMCID: PMC10843279 DOI: 10.1053/j.gastro.2023.09.047] [Citation(s) in RCA: 23] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/10/2023] [Accepted: 09/18/2023] [Indexed: 10/10/2023]
Abstract
Helicobacter pylori is the most common chronic bacterial infection worldwide and the most significant risk factor for gastric cancer, which remains a leading cause of cancer-related death globally. H pylori and gastric cancer continue to disproportionately impact racial and ethnic minority and immigrant groups in the United States. The approach to H pylori case-finding thus far has relied on opportunistic testing based on symptoms or high-risk indicators, such as racial or ethnic background and family history. However, this approach misses a substantial proportion of individuals infected with H pylori who remain at risk for gastric cancer because most infections remain clinically silent. Moreover, individuals with chronic H pylori infection are at risk for gastric preneoplastic lesions, which are also asymptomatic and only reliably diagnosed using endoscopy and biopsy. Thus, to make a significant impact in gastric cancer prevention, a systematic approach is needed to better identify individuals at highest risk of both H pylori infection and its complications, including gastric preneoplasia and cancer. The approach to H pylori eradication must also be optimized given sharply decreasing rates of successful eradication with commonly used therapies and increasing antimicrobial resistance. With growing acceptance that H pylori should be managed as an infectious disease and the increasing availability of susceptibility testing, we now have the momentum to abandon empirical therapies demonstrated to have inadequate eradication rates. Molecular-based susceptibility profiling facilitates selection of a personalized eradication regimen without necessitating an invasive procedure. An improved approach to H pylori eradication coupled with population-level programs for screening and treatment could be an effective and efficient strategy to prevent gastric cancer, especially in minority and potentially marginalized populations that bear the heaviest burden of H pylori infection and its complications.
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Affiliation(s)
- Steven F Moss
- Brown University, Providence, Rhode Island; Providence VA Medical Center, Providence, Rhode Island
| | - Shailja C Shah
- University of California at San Diego, San Diego, California; VA San Diego Healthcare System, San Diego, California
| | - Mimi C Tan
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas.
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Hoshino S, Momma E, Motomiya R, Tanabe T, Koeda M, Hoshikawa Y, Kawami N, Iwakiri K. Characteristics of proton pump inhibitor-resistant severe reflux esophagitis and efficacy of vonoprazan in elderly (older than 75 years) and non-elderly groups. JGH Open 2024; 8:e13023. [PMID: 38268954 PMCID: PMC10805484 DOI: 10.1002/jgh3.13023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 11/29/2023] [Accepted: 12/06/2023] [Indexed: 01/26/2024]
Abstract
Background and Aim Previous studies on age differences in proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) have found that stenosis and bleeding complications were significantly more common in the elderly than in the non-elderly. We sought to examine differences between two groups of elderly (75 years or older) and non-elderly (<75 years) patients with (PPI)-resistant severe RE and also the efficacy of vonoprazan (VPZ) in these patients. Methods There were 14 patients in the elderly group and 15 in the non-elderly group. Information was obtained on patient background (sex, body mass index [BMI], gastric mucosal atrophy, and the presence of hernia and collagen disease), and all patients underwent the saliva secretion test and esophagogastroduodenoscopy (EGD). The saliva secretion test (amount of saliva secreted, salivary pH, and the acid-buffering capacity) was performed by chewing sugar-free gum for 3 min before EGD. The efficacy of VPZ in both groups was also assessed. Results Saliva secretion, sex, BMI, and the presence of gastric mucosal atrophy did not significantly differ between the two groups. The number of hernias larger than 4 cm was significantly higher in the elderly PPI-resistant group, and significantly more patients had collagen disease in the non-elderly group. The efficacy of VPZ was not significantly different between the two groups; however, 10 patients in the non-elderly group had collagen disease, and 4 did not achieve esophageal mucosal healing even with VPZ 20 mg. Conclusion The number of large hernias (>4 cm) was significantly higher in the elderly group, while significantly more non-elderly patients had collagen disease. In the non-elderly group with scleroderma, the efficacy of VPZ 20 mg may not be sufficient.
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Affiliation(s)
- Shintaro Hoshino
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Eri Momma
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Rina Motomiya
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Tomohide Tanabe
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Mai Koeda
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Yoshimasa Hoshikawa
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Noriyuki Kawami
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Katsuhiko Iwakiri
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
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Takahashi M, Takahashi K, Kaneda H, Kawaguchi T, Otori T, Nakamura Y. Analysis of Risk Factors for Febrile Neutropenia in Patients with Small-Cell Lung Cancer Receiving Carboplatin Plus Etoposide Therapy. Oncology 2023; 102:565-573. [PMID: 38160673 PMCID: PMC11216354 DOI: 10.1159/000535822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 12/09/2023] [Indexed: 01/03/2024]
Abstract
INTRODUCTION Febrile neutropenia (FN) is an oncologic emergency requiring immediate empiric antibiotic therapy. Although carboplatin plus etoposide combination chemotherapy is associated with a relatively high frequency of FN, the risk factors are unclear. Hence, this retrospective study aimed to identify predictive markers of carboplatin/etoposide-induced FN. METHODS We conducted a retrospective cohort analysis of patients with previously untreated small-cell lung cancer (SCLC) who received combination chemotherapy with carboplatin (area under the concentration curve: 5 mg/mL·min, day 1) and etoposide (80 or 100 mg/m2, days 1-3) between July 2007 and June 2022. FN was assessed during the 21 days after initiation of carboplatin and etoposide therapy according to the Japanese Society of Medical Oncology's definition. Fisher's exact test for categorical variables and Mann-Whitney U test for continuous variables were used to compare the two groups. Statistical significance was set at p values <0.05. Explanatory variables with p values <0.05 in the univariate analysis were included in the multivariate logistic regression analysis. RESULTS Among the 176 eligible patients, the incidence of FN during the first cycle of chemotherapy was 25.0% (44/176). Multivariate analysis revealed that co-administration of proton pump inhibitors (PPIs) or potassium-competitive acid blockers (PCABs) and body mass index (BMI) were significantly associated with FN (p = 0.0035 and 0.0011, respectively). Patients with both co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 presented with significantly higher frequencies of FN compared with the other patients (13/24 [54.2%] vs. 31/152 [20.4%] patients; odds ratio: 4.56, 95% confidence interval: 1.70-12.48; p = 0.00147). CONCLUSION Patients who received carboplatin plus etoposide for SCLC with co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 more frequently present with FN than those without the two factors.
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Affiliation(s)
- Masaya Takahashi
- Department of Pharmacy, Osaka Metropolitan University Hospital, Osaka, Japan
- Division of Social Pharmacy, Faculty of Pharmacy, Kindai University, Osaka, Japan
| | - Katsuyuki Takahashi
- Division of Social Pharmacy, Faculty of Pharmacy, Kindai University, Osaka, Japan
| | - Hiroyasu Kaneda
- Department of Clinical Oncology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Tomoya Kawaguchi
- Department of Clinical Oncology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Toru Otori
- Division of Social Pharmacy, Faculty of Pharmacy, Kindai University, Osaka, Japan
| | - Yasutaka Nakamura
- Department of Pharmacy, Osaka Metropolitan University Hospital, Osaka, Japan
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Guan JL, Feng LN, Han YY, Xia SH, Zhao K, Zhang MY, Zhang Y, Dong RN, Huang YJ, Li JY, Liao JZ, Li PY. Global research trends and hotspots of Helicobacter pylori eradication based on clinical trial registration platforms: A cross-sectional analysis. Clin Res Hepatol Gastroenterol 2023; 47:102233. [PMID: 37879535 DOI: 10.1016/j.clinre.2023.102233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 10/15/2023] [Accepted: 10/23/2023] [Indexed: 10/27/2023]
Abstract
BACKGROUND This study aimed to obtain an overview of clinical trials on Helicobacter pylori (H. pylori) eradication and analyze the global trends and hotspots in this field. METHODS We collected the data from clinical trials focused on H. pylori eradication in the primary clinical trial registries from 2000 to 2022 in the world. Then we analyzed the research trends and hotspots in H. pylori eradication regimens in different regions at different periods. RESULTS A total of 780 clinical trials were included, which were mainly conducted in Asia (682), followed by Europe (59), Africa (20), North America (16), South America (7), Oceania (2). The most active countries were China (343), Iran (140), South Korea (63), and Japan (73). "Bismuth-containing quadruple therapy (BQT)" was the most studied regimen (159, 20.38 %). Additionally, clinical trials focused on potassium-competitive acid blockers (P-CABs)-based therapy, probiotics, and high-dose dual therapy (HDDT) were constantly increasing. BQT received the most attention in China (26.53 %) and Iran (22.14 %), while it was tailored therapy in South Korea (23.29 %). P-CABs-based therapy was the main reseach hotspot in Japan (61.90 %). CONCLUSION How to eradicate H. pylori infection has been a heated research topic. BQT, P-CABs-based therapy, probiotics, and HDDT attracted the most attention in recent years.
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Affiliation(s)
- Jia-Lun Guan
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li-Na Feng
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ying-Ying Han
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Su-Hong Xia
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kai Zhao
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ming-Yu Zhang
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Zhang
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ruo-Nan Dong
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu-Jie Huang
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ji-Yan Li
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jia-Zhi Liao
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Pei-Yuan Li
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Gastroenterology, Wenchang People's Hospital, Wenchang, China.
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Edelmuth RCL, Riascos MC, Al Asadi H, Greenberg JA, Miranda IC, Najah H, Crawford CV, Schnoll-Sussman FH, Finnerty BM, Fahey TJ, Zarnegar R. Gastric development of pancreatic acinar cell metaplasia after Vonoprazan therapy in rats. Surg Endosc 2023; 37:9366-9372. [PMID: 37644156 DOI: 10.1007/s00464-023-10371-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 07/30/2023] [Indexed: 08/31/2023]
Abstract
BACKGROUND Vonoprazan is a new acid-suppressing drug that received FDA approval in 2022. It reversibly inhibits gastric acid secretion by competing with the potassium ions on the luminal surface of the parietal cells (potassium-competitive acid blockers or P-CABs). Vonoprazan has been on the market for a short time and there are many clinical trials to support its clinical application. However, medical experience and comprehensive clinical data is still limited, especially on how and if, gastric histology is altered due to therapy. METHODS A 12-week experiment trial with 30 Wistar rats was to assess the presence of gastrointestinal morphologic abnormalities upon administration of omeprazole and vonoprazan. At six weeks of age, rats were randomly assigned to one of 5 groups: (1) saline as negative control group, (2) oral omeprazole (40 mg/kg), as positive control group, (3) oral omeprazole (40 mg/kg) for 4 weeks, proceeded by 8 weeks off omeprazole, (4) oral vonoprazan (4 mg/kg), as positive control group, and (5) oral vonoprazan (4 mg/kg) for 4 weeks, proceeded by 8 weeks off vonoprazan. RESULTS We identified non-inflammatory alterations characterized by parietal (oxyntic) cell loss and chief (zymogen) cell hyperplasia and replacement by pancreatic acinar cell metaplasia (PACM). No significant abnormalities were identified in any other tissues in the hepatobiliary and gastrointestinal tracts. CONCLUSION PACM has been reported in gastric mucosa, at the esophagogastric junction, at the distal esophagus, and in Barrett esophagus. However, the pathogenesis of this entity is still unclear. Whereas some authors have suggested that PACM is an acquired process others have raised the possibility of PACM being congenital in nature. Our results suggest that the duration of vonoprazan administration at a dose of 4 mg/kg plays an important role in the development of PACM.
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Affiliation(s)
- Rodrigo C L Edelmuth
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, 525 East 68Th Street, K-836, New York, NY, 10065, USA
- Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Maria Cristina Riascos
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, 525 East 68Th Street, K-836, New York, NY, 10065, USA
| | - Hala Al Asadi
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, 525 East 68Th Street, K-836, New York, NY, 10065, USA
| | - Jacques A Greenberg
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, 525 East 68Th Street, K-836, New York, NY, 10065, USA
| | - Ileana C Miranda
- Laboratory of Comparative Pathology, Weill Cornell Medical College, New York-Presbyterian Hospital, Memorial Sloan Kettering Cancer Center, The Rockefeller University, New York, NY, USA
| | - Haythem Najah
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, 525 East 68Th Street, K-836, New York, NY, 10065, USA
| | - Carl V Crawford
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA
| | - Felice H Schnoll-Sussman
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA
| | - Brendan M Finnerty
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, 525 East 68Th Street, K-836, New York, NY, 10065, USA
| | - Thomas J Fahey
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, 525 East 68Th Street, K-836, New York, NY, 10065, USA
| | - Rasa Zarnegar
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, 525 East 68Th Street, K-836, New York, NY, 10065, USA.
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Kahrilas PJ. Editorial: On-demand vonoprazan for NERD-when should it be 'demanded'? Aliment Pharmacol Ther 2023; 58:1230. [PMID: 37986601 DOI: 10.1111/apt.17737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2023]
Abstract
LINKED CONTENTThis article is linked to Fass et al papers. To view these articles, visit https://doi.org/10.1111/apt.17728 and https://doi.org/10.1111/apt.17766
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Affiliation(s)
- Peter J Kahrilas
- Division of Gastroenterology and Hepatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
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Wang D, Zhou D, Liu X, Xu Z, Bai T, Hou X. Different dosages of vonoprazan for gastroesophageal reflux disease: study protocol for a pragmatic, crossover-cluster, randomized controlled trial with patient preference arms. Trials 2023; 24:778. [PMID: 38041136 PMCID: PMC10691065 DOI: 10.1186/s13063-023-07760-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Accepted: 10/27/2023] [Indexed: 12/03/2023] Open
Abstract
BACKGROUND Vonoprazan results in more potent acid suppression for gastroesophageal reflux disease (GERD) than proton pump inhibitors. It has only been approved for treating erosive esophagitis in China, but 30-40% of GERD patients cannot achieve the goal of treatment with vonoprazan 20 mg daily. This study aims to investigate whether vonoprazan could relieve the symptoms of Chinese patients with non-erosive reflux disease (NERD) and whether increased dosage or different times of dosing could increase the response rate of GERD. METHODS This study is a pragmatic, open-label, crossover-cluster, randomized controlled trial with patient preference arms. Two thousand eight hundred eighty patients with GERD from 48 hospitals in China will be enrolled. These hospitals will be divided into a compulsory randomization cluster (24 hospitals) and a patient preference cluster (24 hospitals). Patients in the compulsory randomization cluster will be randomized to three regimens according to the crossover-cluster randomization. Patients in the patient preference cluster may choose to receive any regimen if they have a preference; otherwise, patients will be randomly assigned. The three treatment regimens will last 4 weeks, including (1) vonoprazan 20 mg p.o. after breakfast, (2) vonoprazan 20 mg p.o. after dinner, and (3) vonoprazan 20 mg p.o. after breakfast and after dinner. Patients will attend a baseline visit, a 4-week e-diary, a fourth-week visit, and a sixth-month visit online. The primary outcome is the symptom relief rate of all patients after 4-week therapy. Secondary outcomes include the healing rate of EE patients, the severity of symptoms, compliance with the therapy at the fourth-week follow-up visit, recurrent symptoms, and the frequency of self-conscious doctor visits at the sixth-month follow-up visit. DISCUSSION This trial will explore the effectiveness of different regimens of vonoprazan that will be implemented with GERD patients in China. The randomization with patient preferences considered and the crossover-cluster component may improve the robustness and extrapolation of study conclusions. TRIAL REGISTRATION https://www.chictr.org.cn ChiCTR2300069857. Registered on 28 March 2023. PROTOCOL VERSION February 18, 2023, Version 2.
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Affiliation(s)
- Dongke Wang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dan Zhou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xinghuang Liu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhiyue Xu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Bai
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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MAZUMDER AVIJIT, KUMAR NAVEEN, DAS SAUMYA. A Comprehensive Review of Gastroesophageal Reflux Disease (GERD) Treatment and its Clinical Perspectives. INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES AND NANOTECHNOLOGY(IJPSN) 2023; 16:7093-7103. [DOI: 10.37285/ijpsn.2023.16.6.9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Gastroesophageal reflux disease (GERD) occurs by regurgitation of food in the stomach. Aggressive factors increase GERD whereas defensive factors decrease GERD progression. GERD if mild can be put under control by lifestyle modification and giving non-pharmacological treatment methods to patients however if the disease progresses non-pharmacological methods are ineffective. Drugs reduce GERD progression and also maintain the pH of the stomach to a normal level and prevent abnormal acid exposure to the oesophagus. Antacids and alginate protect oesophagus by reducing acidity and increasing viscosity. Proton pump inhibitors and histamine 2 receptor antagonists reduce acid secretion by inhibiting its secretion. Prokinetic agents increase the motility of the stomach and reduce obesity. Metabotropic glutamate receptors, gamma-aminobutyric acid receptor agonists, and cannabinoid receptors are receptor-specific drugs that act on receptors underlying the gastrointestinal tract and alter the function of receptors which increases reflux disease. Combination of antacid and alginate, domperidone and omeprazole, omeprazole and baclofen, aluminum hydroxide, magnesium, and simethicone are frequently given in GERD to expedite the healing rate and reduce acid secretion. Combinations of suitable medications reduce the adverse effects of a single medication and also make it therapeutically more effective than using monotherapy drugs. The pharmacological method is safe and effective and treats GERD completely.
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