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Kotelevets SM. Risks of anti- Helicobacter therapy and long-term therapy with antisecretory drugs. World J Gastroenterol 2025; 31:101933. [PMID: 39877710 PMCID: PMC11718649 DOI: 10.3748/wjg.v31.i4.101933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 11/08/2024] [Accepted: 12/06/2024] [Indexed: 12/30/2024] Open
Abstract
Helicobacter pylori (H. pylori) infection has a protective effect on gastroesophageal reflux disease (GERD). Both of these diseases have a very high incidence and prevalence. As a result, GERD often recurs after anti-Helicobacter therapy. The problem of effective treatment of H. pylori infection and GERD is that the main groups of drugs [proton pump inhibitors (PPIs) and potassium-competitive acid blockers] have the possibility of side effects with use. Such supposed side effects have no evidence in randomized controlled trials that comply with the principles of evidence-based medicine. Morphological changes in the gastric mucosa after long-term use of antisecretory drugs should be considered as compensatory mechanisms of sanogenesis. The greatest concern for doctors who treat patients with antisecretory drugs is the risk of gastric carcinogenesis. This article presents an analysis of morphological and pathophysiological changes that occur after long-term use of antisecretory drugs (PPIs). Hypertrophy (hyperplasia) of G cells, enterochromaffin-like cells and possible fundic gland polyps (hyperplasia) are compensatory mechanisms of sanogenesis during long-term treatment with PPIs. These mechanisms are of primary importance for rehabilitation and prevention of complications in patients with GERD, non-steroidal anti-inflammatory drugs-gastropathy and other diseases during long-term treatment with PPIs. Understanding the pathophysiological and morphological mechanisms of compensation and adaptation, the mechanisms of sanogenesis and carcinogenesis will increase the number of indications for long-term use of PPIs with a high level of efficiency and safety of treatment. In addition, understanding the pathophysiological and morphological mechanisms of compensation and adaptation, the mechanisms of sanogenesis will allow us to forecast the side effects of long-term use of potassium-competitive acid blockers.
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Affiliation(s)
- Sergey M Kotelevets
- Department of Therapy, North Caucasus State Academy, Cherkessk 369000, Russia
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2
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Ouyang M, Zou S, Cheng Q, Shi X, Zhao Y, Sun M. Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers vs. Proton Pump Inhibitors for Peptic Ulcer with or without Helicobacter pylori Infection: A Systematic Review and Network Meta-Analysis. Pharmaceuticals (Basel) 2024; 17:698. [PMID: 38931366 PMCID: PMC11206580 DOI: 10.3390/ph17060698] [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: 05/02/2024] [Revised: 05/22/2024] [Accepted: 05/23/2024] [Indexed: 06/28/2024] Open
Abstract
Novel potassium-competitive acid blockers (P-CABs) have emerged as effective acid-suppressive drugs in recent years, replacing proton pump inhibitors (PPIs). We aim to compare the efficacy and safety of P-CABs versus PPIs in the treatment of peptic ulcers with or without Helicobacter pylori (H. pylori) infection. We searched in PubMed, Embase, WOS, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases (all years up to January 2024). Efficacy and safety outcomes were evaluated using odds ratio (OR) and 95% confidence intervals (CI). The Surface Under the Cumulative Ranking (SUCRA) probabilities were used to rank each intervention. Among 14,056 studies screened, 56 studies involving 9792 participants were analyzed. Vonoprazan demonstrated the best efficacy in ulcer healing rate and H. pylori eradication rate (SUCRA = 86.4% and 90.7%, respectively). Keverprazan ranked second in ulcer healing rates (SUCRA = 76.0%) and was more effective in pain remission rates (SUCRA = 91.7%). The risk of adverse events was low for keverprazan (SUCRA = 11.8%) and tegoprazan (SUCRA = 12.9%), and moderate risk for vonoprazan (SUCRA = 44.3%) was demonstrated. Compared to lansoprazole, vonoprazan exhibited a higher risk of drug-related adverse events (OR: 2.15; 95% CI: 1.60-2.89) and serious adverse events (OR: 2.22; 95% CI: 1.11-4.42). Subgroup analysis on patients with H. pylori-positive peptic ulcers showed that vonoprazan was at the top of the SUCRA rankings, followed by keverprazan. Vonoprazan showed superior performance in peptic ulcers, especially for patients with H. pylori-positive peptic ulcers. However, the risk of adverse events associated with vonoprazan should be noted. Keverprazan has also shown good therapeutic outcomes and has performed better in terms of safety.
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Affiliation(s)
| | | | | | | | | | - Minghui Sun
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China; (M.O.); (S.Z.); (Q.C.); (X.S.); (Y.Z.)
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3
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Muhammad HJ, Shimada T, Fujita A, Sai Y. Sodium citrate buffer improves pazopanib solubility and absorption in gastric acid-suppressed rat model. Drug Metab Pharmacokinet 2024; 55:100995. [PMID: 38447327 DOI: 10.1016/j.dmpk.2024.100995] [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: 09/01/2023] [Revised: 11/24/2023] [Accepted: 12/29/2023] [Indexed: 03/08/2024]
Abstract
Pazopanib exhibits pH-dependent solubility and its absorption depends primarily on the stomach pH. Significant decrease of pazopanib absorption by coadministration with proton pump inhibitors in clinical situation need to be overcome. Thus, the purpose of this study is firstly to investigate the effect of acidic beverages and sodium citrate buffer on the solubility of pazopanib and secondly to examine the effect of sodium citrate buffer on pazopanib absorption in a rat model with esomeprazole-mediated gastric acid suppression. Pazopanib solubility decreased with increasing pH of sodium citrate buffer in vitro. Interestingly, its solubility in some acidic beverages was significantly lower than that in sodium citrate buffer of the same pH. The AUC0-24h of pazopanib administered in tap water to rats treated with esomeprazole (ESP rats) was 66 % lower than that in the control rats treated with saline. However, AUC0-24h was 4.8 times higher in ESP rats that received pazopanib with sodium citrate buffer (pH 2.3) compared to ESP rats that received pazopanib with tap water. Our results indicate that the drug-drug interactions between pazopanib and proton pump inhibitors can be overcome, at least in part, by suspending pazopanib in sodium citrate buffer.
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Affiliation(s)
- Huda Jassim Muhammad
- Department of Clinical Pharmacokinetics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan; Department of Clinical Pharmacy, College of Pharmacy, Karbala University, Karbala, 56001, Iraq.
| | - Tsutomu Shimada
- Department of Clinical Pharmacokinetics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan; Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
| | - Arimi Fujita
- Department of Clinical Pharmacokinetics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan; Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
| | - Yoshimichi Sai
- Department of Clinical Pharmacokinetics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan; Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
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Fang Y, He X, Peng A, Yang YQ, Xiang J. Association Study of Esomeprazole Pharmacokinetics and CYP2C19 Gene Polymorphisms. Clin Pharmacol Drug Dev 2024; 13:134-139. [PMID: 37772804 DOI: 10.1002/cpdd.1334] [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: 06/24/2023] [Accepted: 08/30/2023] [Indexed: 09/30/2023]
Abstract
To investigate the association between esomeprazole pharmacokinetics and CYP2C19 gene polymorphisms in a cohort of 95 healthy Chinese participants. A cohort of 95 participants was assembled and stratified into 2 distinct groups, receiving either 20 or 40 mg of esomeprazole through oral administration. The subjects encompassed 17 poor metabolizers, 47 intermediate metabolizers, and 31 rapid metabolizers, and their genotypes were ascertained using the polymerase chain reaction-restriction fragment length polymorphism technique. Esomeprazole plasma concentrations were quantified employing a high-performance liquid chromatography-ultraviolet method. Pharmacokinetic parameters were computed via Phoenix WinNonlin 6.1 software, while SPSS 26.0 facilitated statistical analysis to contrast the pharmacokinetics and the CYP2C19 genotypes. In the aftermath of administering 20 or 40 mg esomeprazole, marked differences were discerned between terminal elimination half-life, maximum concentration/dose, and area under the plasma concentration-time curve from time zero to infinity/dose of esomeprazole (P < .05), with the exception of time to maximum concentration. The findings of this investigation signify a significant association between esomeprazole metabolism and CYP2C19 gene polymorphisms. There were no unprecedented adverse events documented subsequent to the administration of 20 and 40 mg esomeprazole dosages. Esomeprazole has manifested promising safety and tolerability profiles in pertinent clinical trials.
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Affiliation(s)
- Yuan Fang
- Department of Gastroenterology, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
- Department of Clinical Research Management, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
| | - Xia He
- Department of Gastroenterology, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
- Department of Clinical Research Management, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
- Clinical Trial Center, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
- NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
| | - Ai Peng
- Department of Gastroenterology, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
- Department of Clinical Research Management, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
- Clinical Trial Center, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
- NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
| | - Yi Qi Yang
- Department of Forensic Toxicological Analysis, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Wuhou, Chengdu, P.R. China
| | - Jin Xiang
- Department of Gastroenterology, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
- Department of Clinical Research Management, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
- Clinical Trial Center, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
- NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, West China Hospital, Sichuan University, Wuhou, Chengdu, P.R. China
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Hofmann J, Bartůněk A, Hauser T, Sedmak G, Beránek J, Ryšánek P, Šíma M, Slanař O. Dasatinib anhydrate containing oral formulation improves variability and bioavailability in humans. Leukemia 2023; 37:2486-2492. [PMID: 37789147 PMCID: PMC10681895 DOI: 10.1038/s41375-023-02045-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 09/11/2023] [Accepted: 09/19/2023] [Indexed: 10/05/2023]
Abstract
Dasatinib monohydrate indicated for the treatment of chronic myeloid leukemia displays pH-dependent solubility. The aim of reported development program of novel dasatinib anhydrate containing formulation was to demonstrate improved absorption and lower pharmacokinetic variability compared to dasatinib monohydrate. In a bioavailability study comparing formulations containing 110.6 mg and 140 mg of dasatinib as anhydrate and monohydrate, respectively, both Cmax and AUC of dasatinib were within standard 80.00-125.00% range, while the intra- and inter-subject variability for AUC0-inf after the test product was approximately 3-fold and 1.5-fold less than after the reference, respectively.In a drug-drug interaction study, omeprazole 40 mg reduced the mean AUC0-inf of dasatinib by 19%, when the test was ingested 2 h before the 5th omeprazole dose. This decrease of exposure is clinically irrelevant and substantially less than after the reference. Co-prescription analysis supports the importance of pH-dependent solubility of dasatinib, as >21% of patients were treated concomitantly with a PPI and dasatinib despite warnings against this co-medication in the SmPC.The novel dasatinib anhydrate containing formulation demonstrated improved absorption and less pharmacokinetic variability compared to dasatinib monohydrate product, which may translate into improved clinical outcomes, although this needs to be proven by an appropriate trial.
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Affiliation(s)
| | - Aleš Bartůněk
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | | | | | | | - Pavel Ryšánek
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Martin Šíma
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
| | - Ondřej Slanař
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
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Lin WY, Wang SS, Kang YN, Porpiglia AS, Chang Y, Huang CH, Bhimani R, Abdul-Lattif E, Azmat M, Wang TH, Lin YS, Chang YC, Chi KY. Do proton pump inhibitors affect the effectiveness of chemotherapy in colorectal cancer patients? A systematic review with meta-analysis. Front Pharmacol 2022; 13:1048980. [PMID: 36578549 PMCID: PMC9792119 DOI: 10.3389/fphar.2022.1048980] [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: 09/20/2022] [Accepted: 11/25/2022] [Indexed: 12/14/2022] Open
Abstract
Proton pump inhibitors (PPI), one of the most commonly prescribed medications, carry a myriad of adverse events. For colorectal cancer (CRC) patients, it still remains unclear whether the concurrent use of proton pump inhibitors (PPI) would negatively affect chemotherapy. PubMed, Medline, Embase, and Cochrane Library were searched from inception to 10 June 2022, to identify relevant studies involving CRC patients receiving chemotherapy and reporting comparative survival outcomes between PPI users and non-users. Meta-analyses were performed using random-effects models. We identified 16 studies involving 8,188 patients (PPI = 1,789; non-PPI = 6,329) receiving either capecitabine-based or fluorouracil-based regimens. The overall survival (HR, 1.02; 95% CI, 0.91 to 1.15; I2 = 0%) and progression-free survival (HR, 1.15; 95% CI, 0.98 to 1.35; I2 = 29%) were similar between PPI users and non-users in patients taking capecitabine-based regimens, with low statis-tical heterogeneity. Although the subgroup analysis indicated that early-stage cancer patients taking capecitabine monotherapy with concurrent PPI had a significantly higher disease progression rate (HR, 1.96; 95% CI, 1.21 to 3.16; I2 = 0%) than those who did not use PPIs, both groups had comparable all-cause mortality (HR, 1.31; 95% CI, 0.75 to 2.29; I2 = 0%). On the other hand, there was little difference in both OS and PFS in both early- and end-stage patients taking capecitabine combination therapy between PPI users and non-users. Conversely, the use of concomitant PPI in patients taking fluorouracil-based regimens contributed to a marginally significant higher all-cause mortality (HR, 1.18; 95% CI, 1.00 to 1.40; I2 = 74%), but with high statistical heterogeneity. In conclusion, PPI has little survival influence on CRC patients treated with capecitabine-based regimens, especially in patients taking capecitabine combination therapy. Thus, it should be safe for clinicians to prescribe PPI in these patients. Although patients treated with fluorouracil-based regimens with concomitant PPI trended toward higher all-cause mortality, results were subject to considerable heterogeneity. Systematic Review Registration: identifier https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022338161.
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Affiliation(s)
- Wan-Ying Lin
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Shih-Syuan Wang
- Department of Education, Center for Evidence-Based Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Yi-No Kang
- Department of Education, Center for Evidence-Based Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Andrea S. Porpiglia
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, United States
| | - Yu Chang
- Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chin-Hsuan Huang
- Department of Education, Center for Evidence-Based Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Ronak Bhimani
- Department of Internal Medicine, Lower Bucks Hospital, Bristol, PA, United States
| | - Eahab Abdul-Lattif
- Department of Internal Medicine, Lower Bucks Hospital, Bristol, PA, United States
| | - Muneeba Azmat
- Department of Internal Medicine, Lower Bucks Hospital, Bristol, PA, United States
| | - Tsu-Hsien Wang
- Department of Education, Center for Evidence-Based Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Yu-Shiuan Lin
- Department of Education, Center for Evidence-Based Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Yu-Cheng Chang
- Department of Education, Center for Evidence-Based Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Kuan-Yu Chi
- Department of Education, Center for Evidence-Based Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
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7
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Douwes RM, Vinke JSJ, Gomes-Neto AW, Ayerdem G, van Hassel G, Berger SP, Touw DJ, Blokzijl H, Bakker SJL, de Borst MH, Eisenga MF. Type of proton-pump inhibitor and risk of iron deficiency in kidney transplant recipients - results from the TransplantLines Biobank and Cohort Study. Transpl Int 2021; 34:2305-2316. [PMID: 34519109 PMCID: PMC9293430 DOI: 10.1111/tri.14110] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 08/16/2021] [Accepted: 09/03/2021] [Indexed: 12/16/2022]
Abstract
Proton‐pump inhibitors (PPIs) have been associated with iron deficiency (ID) in kidney transplant recipients (KTRs). Gastric acid plays a pivotal role in the intestinal absorption of non‐heme iron, but the pharmacodynamics of PPIs differs in potency of acid suppression. We hypothesized that the risk of ID might be lower in KTRs using a less potent PPI. In a cohort of 724 KTRs from the TransplantLines Biobank and Cohort Study (NCT03272841), PPI use was associated with ID [odds ratio (OR) 2.02; 95% CI 1.36–2.98]. Compared with no PPI use, the point estimate of the odds ratio for risk of ID for pantoprazole (OR 1.55; 95%CI 0.78–3.10) was lower than for esomeprazole and omeprazole (3.58; 95%CI 1.73–7.40 and 1.96; 95%CI 1.31–2.94, respectively). When comparing pantoprazole users with omeprazole users on an equipotent dose (≤20 omeprazole equivalents (OE)/day) omeprazole, but not pantoprazole was associated with ID, although the lack of a significant effect of pantoprazole on the risk of ID could be caused by a lack of power. Furthermore, risk of ID was higher among users of a high PPI dose (≥ 20 OE/day) and OE as continuous variable was also independently associated with ID, indicating that risk of ID is higher while using a more potent PPI. Further investigation seems warranted to confirm whether pantoprazole leads to less ID in KTRs.
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Affiliation(s)
- Rianne M Douwes
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Joanna Sophia J Vinke
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - António W Gomes-Neto
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Gizem Ayerdem
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Gaston van Hassel
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Stefan P Berger
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Daan J Touw
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Hans Blokzijl
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Stephan J L Bakker
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Martin H de Borst
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Michele F Eisenga
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Al-Eitan LN, Almomani FA, Al-Khatib SM. Association of CYP2C19, TNF-α, NOD1, NOD2, and PPARγ polymorphisms with peptic ulcer disease enhanced by Helicobacter pylori infection. Saudi Med J 2021; 42:21-29. [PMID: 33399167 PMCID: PMC7989310 DOI: 10.15537/smj.2021.1.25654] [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] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVES To assess the correlation between a number of genetic variations of CYP2C19, TNF-α, NOD1, NOD2, and PPARγ genes with the severity of Helicobacter pylori (H. pylori) infections and peptic ulcers (PU). METHODS A retrospective cross-sectional design was used in this study. Formalin-fixed paraffin-embedded (FFPE) tissue was used to extract genomic DNA that was collected from Jordanian patients who visited endoscopy clinics between 2014 to 2018 at the King Abdullah University Hospital (KAUH), Irbid, Jordan. Genotyping of the studied single nucleotide polymorphisms (SNPs) were applied using the sequencing protocol. Results: A total of 251 patients (mean age: 42.12 ± 16.09 years) and healthy controls (mean age: 52.76 ± 19.45 years) were enrolled in this study. This study showed no significant association between patients and the studied polymorphisms except for rs2075820 of the NOD1 (p=0.0046). It is hypothesized that the heterozygous genotype (TC); 44.8% in patients versus 61.3% in controls has a decreased risk of peptic ulcers (OR: 0.49). The alleles frequency association was insignificant in all studied SNPs with a p-value more than 0.05. CONCLUSION This study provided evidence regarding the association of the rs2075820 with H. pylori infections. The other studied SNPs were not statistically significant.
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Affiliation(s)
- Laith N Al-Eitan
- Department of Biotechnology & Genetic Engineering, Faculty of Science and Arts, Jordan University of Science and Technology, Irbid, Jordan. E-mail.
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9
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Ke H, Li J, Lu B, Yang C, Wang J, Wang Z, Liu L, Chen Y. The appropriate cutoff gastric pH value for Helicobacter pylori eradication with bismuth-based quadruple therapy. Helicobacter 2021; 26:e12768. [PMID: 33089598 DOI: 10.1111/hel.12768] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 09/29/2020] [Accepted: 10/01/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND This study aimed to investigate whether an increased proton pump inhibitor (PPI) dose enhanced the efficacy of Helicobacter pylori (H. pylori) eradication and determine the appropriate cutoff intragastric pH value that could predict H. pylori eradication with bismuth-based quadruple therapy. MATERIALS AND METHODS A total of 207 H. pylori infected, treatment naive patients were enrolled in this prospective, open-label, randomized controlled trial. Patients were randomly allocated into Eso40-group (esomeprazole 40 mg bid) and Eso20-group (esomeprazole 20 mg bid), and their CYP2C19 genotyping status was assessed. The 24-h intragastric pH monitoring on day 7 was performed, and percentage of time gastric pH ≥ 3, ≥4, ≥5, and ≥6 (pH holding time ratios; HTRs) were measured. H. pylori eradication was evaluated using 13 C-urea breath test. RESULTS No significant difference in the eradication rates was observed between two groups. The median 24-h intragastric pH value was not significant different between two groups but the Eso40 Group had a significant higher pH4 HTRs (91.11% [95%CI: 87.50%-95.83%] vs. 95.83% [95.83%-100%]; p = .002). Additionally, the median 24-h intragastric pH value showed significantly difference between two groups in EM genotype (Eso20 Group 6.00 [95%CI; 5.75-6.15] vs. Eso40 Group 6.30 [6.05-6.30]; p = .019). Similar results were observed in pH4 HTRs. There were significant differences in intragastric pH value (6.10 [95%CI: 4.40-7.00] vs. 5.65 [4.85-5.95], p = .038) and in pH4 HTRs (96% [95%CI: 92.00%-96.00%] vs. 87.5% [67.00%-100.0%], p = .019) between eradication-successful and eradication-failed patients. Statistical analysis suggested that the median intragastric pH = 5.7 could identify the success of H. pylori eradication. CONCLUSIONS Bismuth-based quadruple therapy resulted in high H. pylori eradication rates either in PPI standard or double doses. Double dose of esomeprazole is associated with better intragastric acid suppression. A median 24-h intragastric pH of 5.7 could be appropriate cutoff value for predicting the successful H. pylori eradication.
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Affiliation(s)
- Haoran Ke
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jing Li
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Bingyun Lu
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Chenghai Yang
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jiamin Wang
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Department of Gastroenterology, University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen, China
| | - Zhiqing Wang
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Le Liu
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ye Chen
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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10
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Douwes RM, Gomes-Neto AW, Eisenga MF, Vinke JSJ, de Borst MH, van den Berg E, Berger SP, Touw DJ, Hak E, Blokzijl H, Navis G, Bakker SJL. Chronic Use of Proton-Pump Inhibitors and Iron Status in Renal Transplant Recipients. J Clin Med 2019; 8:E1382. [PMID: 31484461 PMCID: PMC6780301 DOI: 10.3390/jcm8091382] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 08/28/2019] [Indexed: 02/06/2023] Open
Abstract
Proton-pump inhibitor (PPI) use may influence intestinal iron absorption. Low iron status and iron deficiency (ID) are frequent medical problems in renal transplant recipients (RTR). We hypothesized that chronic PPI use is associated with lower iron status and ID in RTR. Serum iron, ferritin, transferrin saturation (TSAT), and hemoglobin were measured in 646 stable outpatient RTR with a functioning allograft for ≥ 1 year from the "TransplantLines Food and Nutrition Biobank and Cohort Study" (NCT02811835). Median time since transplantation was 5.3 (1.8-12.0) years, mean age was 53 ± 13 years, and 56.2% used PPI. In multivariable linear regression analyses, PPI use was inversely associated with serum iron (β = -1.61, p = 0.001), natural log transformed serum ferritin (β = -0.31, p < 0.001), TSAT (β = -2.85, p = 0.001), and hemoglobin levels (β = -0.35, p = 0.007), independent of potential confounders. Moreover, PPI use was independently associated with increased risk of ID (Odds Ratio (OR): 1.57; 95% Confidence Interval (CI )1.07-2.31, p = 0.02). Additionally, the odds ratio in RTR taking a high PPI dose as compared to RTR taking no PPIs (OR 2.30; 95% CI 1.46-3.62, p < 0.001) was higher than in RTR taking a low PPI dose (OR:1.78; 95% CI 1.21-2.62, p= 0.004). We demonstrated that PPI use is associated with lower iron status and ID, suggesting impaired intestinal absorption of iron. Moreover, we found a stronger association with ID in RTR taking high PPI dosages. Use of PPIs should, therefore, be considered as a modifiable cause of ID in RTR.
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Affiliation(s)
- Rianne M Douwes
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
| | - António W Gomes-Neto
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
| | - Michele F Eisenga
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
| | - Joanna Sophia J Vinke
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
| | - Martin H de Borst
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
| | - Else van den Berg
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
| | - Stefan P Berger
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
| | - Daan J Touw
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
| | - Eelko Hak
- Unit PharmacoTherapy, -Epidemiology and -Economics, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands.
| | - Hans Blokzijl
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
| | - Gerjan Navis
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
| | - Stephan J L Bakker
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
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11
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de Man FM, Hussaarts KGAM, de With M, Oomen-de Hoop E, de Bruijn P, van Halteren HK, van der Burg-de Graauw NCHP, Eskens FALM, van Gelder T, van Leeuwen RWF, Mathijssen RHJ. Influence of the Proton Pump Inhibitor Esomeprazole on the Bioavailability of Regorafenib: A Randomized Crossover Pharmacokinetic Study. Clin Pharmacol Ther 2019; 105:1456-1461. [PMID: 30570132 PMCID: PMC6593619 DOI: 10.1002/cpt.1331] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 11/27/2018] [Indexed: 11/27/2022]
Abstract
Regorafenib exposure could potentially be influenced by an interaction with acid‐reducing drugs. In this crossover trial, patients were randomized into two sequence groups consisting of three phases: regorafenib intake alone, regorafenib with concomitant esomeprazole, and regorafenib with esomeprazole 3 hours prior. The primary end point was the relative difference (RD) in geometric means for regorafenib 0–24‐hour area under the concentration‐time curve (AUC0–24h) and was analyzed by a linear mixed model in 14 patients. AUC0–24h for regorafenib alone was 55.9 μg·hour/mL (coefficient of variance (CV): 40%), and for regorafenib with concomitant esomeprazole or with esomeprazole 3 hours prior AUC0–24h was 53.7 μg·hour/mL (CV: 34%) and 53.6 μg·hour/mL (CV: 43%), respectively. No significant differences were identified when regorafenib alone was compared with regorafenib with concomitant esomeprazole (RD: −3.9%; 95% confidence interval (CI): −20.5 to 16.1%; P = 1.0) or regorafenib with esomeprazole 3 hours prior (RD: −4.1%; 95% CI: −22.8 to 19.2%; P = 1.0). These findings indicate that regorafenib and esomeprazole can be safely combined in clinical practice.
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Affiliation(s)
- Femke M de Man
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Koen G A M Hussaarts
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Mirjam de With
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Esther Oomen-de Hoop
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Peter de Bruijn
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Henk K van Halteren
- Department of Internal Medicine, Admiraal de Ruyter Hospital, Goes, The Netherlands
| | | | - Ferry A L M Eskens
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Teun van Gelder
- Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Roelof W F van Leeuwen
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.,Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Ron H J Mathijssen
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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12
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van Leeuwen RWF, Jansman FGA, Hunfeld NG, Peric R, Reyners AKL, Imholz ALT, Brouwers JRBJ, Aerts JG, van Gelder T, Mathijssen RHJ. Tyrosine Kinase Inhibitors and Proton Pump Inhibitors: An Evaluation of Treatment Options. Clin Pharmacokinet 2018; 56:683-688. [PMID: 28101705 PMCID: PMC5488129 DOI: 10.1007/s40262-016-0503-3] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Tyrosine kinase inhibitors (TKIs) have rapidly become an established factor in oncology, and have been shown to be effective in a wide variety of solid and hematologic malignancies. Use of the oral administration route of TKIs offers flexibility and is convenient for the patient; however, despite these advantages, the oral route of administration also causes a highly relevant new problem. Acid-inhibitory drugs, such as proton pump inhibitors (PPIs), increase the intragastric pH, which may subsequently decrease TKI solubility, bioavailability, and treatment efficacy. Clear and practical advice on how to manage PPI use during TKI therapy is currently not available in the literature. Since PPIs are extensively used during TKI therapy, prescribers are presented with a big dilemma as to whether or not to continue the combined treatment, resulting in patients possibly being deprived of optimal therapy. When all pharmacological characteristics and data of either TKIs and PPIs are considered, practical and safe advice on how to manage this drug combination can be given.
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Affiliation(s)
- Roelof W F van Leeuwen
- Department of Medical Oncology, Erasmus MC Cancer InstituteErasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. .,Department of Hospital Pharmacy, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
| | - Frank G A Jansman
- Department of Clinical Pharmacy, Deventer Hospital, Nico Bolkesteinlaan 75, 7416 SE, Deventer, The Netherlands.,Department of Pharmacotherapy, Epidemiology and Economics, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands
| | - Nicole G Hunfeld
- Department of Hospital Pharmacy, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.,Department of Intensive Care, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands
| | - Robert Peric
- Department of Pulmonary Medicine, Erasmus MC Cancer Institute, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands
| | - Anna K L Reyners
- Department of Medical Oncology, University Medical Center Groningen, A. Deusinglaan 1, 9712 CP, Groningen, The Netherlands
| | - Alex L T Imholz
- Department of Medical Oncology, Deventer Hospital, Nico Bolkesteinlaan 75, 7416 SE, Deventer, The Netherlands
| | - Jacobus R B J Brouwers
- Department of Pharmacotherapy, Epidemiology and Economics, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands
| | - Joachim G Aerts
- Department of Pulmonary Medicine, Erasmus MC Cancer Institute, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands
| | - Teun van Gelder
- Department of Hospital Pharmacy, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.,Department of Internal Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands
| | - Ron H J Mathijssen
- Department of Medical Oncology, Erasmus MC Cancer InstituteErasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands
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13
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Karaca RO, Kalkisim S, Altinbas A, Kilincalp S, Yuksel I, Goktas MT, Yasar U, Bozkurt A, Babaoglu MO. Effects of Genetic Polymorphisms of Cytochrome P450 Enzymes and MDR1 Transporter on Pantoprazole Metabolism and Helicobacter pylori Eradication. Basic Clin Pharmacol Toxicol 2017; 120:199-206. [PMID: 27611887 DOI: 10.1111/bcpt.12667] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Accepted: 08/28/2016] [Indexed: 02/05/2023]
Abstract
Pantoprazole is a proton pump inhibitor that is commonly used in the treatment of peptic ulcer disease (PUD) and metabolized by cytochrome P450 (CYP) enzymes CYP2C19 and CYP3A4. Pantoprazole is a substrate for multi-drug resistance protein 1 (MDR1). Single nucleotide polymorphisms (SNPs) in CYP2C19, CYP3A4 and MDR1 affect enzyme activity or gene expression of proteins and may alter plasma pantoprazole concentrations and treatment success in PUD. In this study, we aimed to investigate the association between genetic polymorphisms in CYP2C19, CYP3A4 and MDR1 and pharmacokinetics of pantoprazole and therapeutic outcome in patients with either Helicobacter pylori-associated [H.P.(+)]-PUD or [H.P.(+)]-gastritis. The plasma pantoprazole concentrations were determined by using an HPLC method at the third hour after a 40-mg tablet of pantoprazole administration in 194 newly diagnosed patients with either [H.P.(+)]-PUD or [H.P.(+)]-gastritis. Genotyping was performed by using PCR-RFLP and DNA sequencing. Among patients appearing for follow-up examination (n = 105), the eradication rate for H. pylori was 82.8% (n = 87). The median pantoprazole plasma concentrations in poor metabolizers (PM), rapid metabolizers (RM) and ultrarapid metabolizers (URM) were 2.07, 1.69 and 1.28 μg/ml, respectively (p = 0.04). CYP3A4*1G and *22 polymorphisms did not affect plasma pantoprazole concentrations and H. pylori eradication rate. The MDR1 genetic polymorphisms did not affect plasma pantoprazole concentrations. MDR1 3435CC-2677GG-1236CC haplotype carriers had lower H. pylori eradication rate (60%) than the remaining subjects (84.9%) while the difference was not statistically significant (p = 0.07). In conclusion, while CYP2C19 genetic polymorphisms significantly affected plasma pantoprazole concentrations, polymorphisms of CYP2C19, CYP3A4 and MDR1 did not affect H. pylori eradication rates.
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Affiliation(s)
- R Ozgur Karaca
- Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Said Kalkisim
- Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Akif Altinbas
- Gastroenterology Unit, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey
| | - Serta Kilincalp
- Gastroenterology Unit, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey
| | - Ilhami Yuksel
- Gastroenterology Unit, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey
| | - Mustafa T Goktas
- Department of Pharmacology, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey
| | - Umit Yasar
- Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Atilla Bozkurt
- Department of Pharmacology, Faculty of Medicine, BAU International University, Batumi, Georgia
| | - Melih O Babaoglu
- Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
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14
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Xuan JW, Song RL, Xu GX, Lu WQ, Lu YJ, Liu Z. Modeling the cost-effectiveness of ilaprazole versus omeprazole for the treatment of newly diagnosed duodenal ulcer patients in China. J Med Econ 2016; 19:1056-1060. [PMID: 27223846 DOI: 10.1080/13696998.2016.1194277] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To evaluate the cost-effectiveness of 10 mg ilaprazole once-daily vs 20 mg omeprazole once-daily to treat newly-diagnosed duodenal ulcer patients in China. METHODS A decision tree model was constructed and the treatment impact was projected up to 1 year. The CYP2C19 polymorphism distribution in the Chinese population, the respective cure rates in the CYP2C19 genotype sub-groups, the impact of Duodenal Ulcer (DU) on utility value and drug-related side-effect data were obtained from the literature. The total costs of medications were calculated to estimate the treatment costs based on current drug retail prices in China. Expert surveys were conducted when published data were not available. Probabilistic sensitivity analysis was performed to gauge the robustness of the results. RESULTS Ilaprazole, when compared with omeprazole, achieved a better overall clinical efficacy. For the overall population, ilaprazole achieved an incremental cost effectiveness ratio (ICER) of ¥132 056 per QALY gained. This is less than the WHO recommended threshold of 3-times the average GDP per capita in China (2014). Furthermore, sub-group analysis showed that ilaprazole is cost-effective in every province in CYP2C19 hetEM patients and in the most developed provinces in CYP2C19 homEM patients. Probabilistic sensitivity analysis suggests that the results are robust with 97% probability that ilaprozole is considered cost-effective when a threshold of 3-times China's average GDP per capita is considered. LIMITATION This study didn't have the data of ilaprazole combined with Hp eradication therapy. Caution should be taken when extrapolating these findings to DU patients with an Hp eradication therapy. CONCLUSIONS The cost-effectiveness analysis results demonstrated that ilaprazole would be considered a cost-effective therapy, compared with omeprazole, in Chinese DU patients based on the efficacy projections in various CYP2C19 polymorphism types.
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Affiliation(s)
- J W Xuan
- a Health Economic Research Institute, Sun Yat-Sen University , Guangzhou , PR China
| | - R L Song
- b Research Center of National Drug Policy & Ecosystem, China Pharmaceutical University , Nanjing , PR China
| | - G X Xu
- c Livzon Pharmaceutical Group Inc. , Shenzhen , PR China
| | - W Q Lu
- c Livzon Pharmaceutical Group Inc. , Shenzhen , PR China
| | - Y J Lu
- d Shanghai Centennial Scientific Co. Ltd , Shanghai , PR China
| | - Z Liu
- c Livzon Pharmaceutical Group Inc. , Shenzhen , PR China
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15
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Deshpande N, V S, V V RK, H V V M, M S, Banerjee R, Tandan M, D NR. Rapid and ultra-rapid metabolizers with CYP2C19*17 polymorphism do not respond to standard therapy with proton pump inhibitors. Meta Gene 2016; 9:159-64. [PMID: 27419077 PMCID: PMC4932617 DOI: 10.1016/j.mgene.2016.06.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Revised: 06/03/2016] [Accepted: 06/17/2016] [Indexed: 02/08/2023] Open
Abstract
Introduction and objective Polymorphisms in genes encoding drug metabolizing enzymes may lead to varied enzyme activity and inter-individual variability in drug efficacy and/or toxicity. Since CYP2C19 and CYP3A4 genes code for enzymes involved in metabolizing wide variety of drugs including proton pump inhibitors, we sought to identify polymorphisms in these genes in order to study their impact on drug metabolism in subjects. Methods DNA was isolated from healthy individuals including tribals and genotyped for 11 single nucleotide polymorphisms in CYP2C19 and 6 polymorphisms in CYP3A4. Individuals were categorized into different phenotypes based on their drug metabolizing genotype. Volunteers from each group were administered proton pump inhibitors (Esomeprazole, Pantoprazole; 40 mg/day) for 5 days followed by pharmacokinetic studies and measurement of intra-gastric pH. Results Of the 17 polymorphisms studied, only CYP2C19*2,*3,*17 and CYP3A4*1B polymorphisms were observed. In comparison to urban individuals, a significantly (p = 0.0003) higher number of poor metabolizers were noted in the tribal individuals. Pantoprazole was found to be most effective in poor metabolizers in terms of area under the curve and Tmax. No significant difference was observed in the intra-gastric pH at baseline and day 6 in rapid and ultra-rapid metabolizers. Conclusion Our study has demonstrated that 19.7% of our subjects are carriers of the CYP2C19*17 allele who did not respond to the standard dose of proton pump inhibitors. Genetic screening to identify subjects with variant alleles would thus be useful for personalization of therapy with proton pump inhibitors.
Frequency of poor metabolizers varies significantly in two distinct ethnic groups studied. Subjects with CYP2C19*17 polymorphism are not responsive to standard PPI dose. Identifying individuals with these variants may aid in tailoring drug dose for hyper acidic conditions.
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Affiliation(s)
- Neha Deshpande
- Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad 500082, Telangana, India
| | - Sharanya V
- Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad 500082, Telangana, India
| | - Ravi Kanth V V
- Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad 500082, Telangana, India
| | - Murthy H V V
- Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad 500082, Telangana, India
| | - Sasikala M
- Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad 500082, Telangana, India
| | - Rupa Banerjee
- Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082, Telangana, India
| | - Manu Tandan
- Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082, Telangana, India
| | - Nageshwar Reddy D
- Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082, Telangana, India
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16
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Hong J, Shu X, Liu D, Zhu Y, Xie C, Xie Y, Zhang K, Wang A, Xiong H, Zeng H, Yu H, Ma J, Chen Y, Zhu X, Lu N. Antibiotic resistance and CYP2C19 polymorphisms affect the efficacy of concomitant therapies for Helicobacter pylori infection: an open-label, randomized, single-centre clinical trial. J Antimicrob Chemother 2016; 71:2280-5. [PMID: 27107097 DOI: 10.1093/jac/dkw118] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2016] [Accepted: 03/09/2016] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES We evaluate the efficacy of concomitant therapy for Helicobacter pylori infection and the associated factors that influence it in China, where it has not previously been investigated. METHODS In this prospective study, 374 consecutive patients with H. pylori infection were randomly assigned to 10 day regimens of concomitant therapy with different proton pump inhibitors: esomeprazole (20 mg)/omeprazole (20 mg), amoxicillin (1000 mg), clarithromycin (500 mg) and metronidazole (400 mg). All drugs were administered twice daily. A [(13)C]urea breath test was performed at least 4 weeks after the completion of treatment. Gene polymorphisms and antimicrobial susceptibility were determined. RESULTS A total of 374 patients with active, uncomplicated duodenal ulcer disease were enrolled in the study (187 cases in each group). The overall eradication rate resulting from concomitant therapy was 90.7% (PP) and 86.1% (ITT) and the eradication rate was significantly higher in the group that received an esomeprazole-based regimen compared with the group that received an omeprazole-based regimen [95.4% versus 86.0%, respectively, P = 0.003 (PP) and 89.8% versus 82.4%, P = 0.036 (ITT), respectively]. Moreover, the omeprazole-based regimen was an independent risk factor for treatment failure (P = 0.039), as were CYP2C19 extensive metabolizer (P = 0.005), clarithromycin (P = 0.000) and metronidazole resistance (P = 0.000). In addition, CYP2C19 polymorphisms and antibiotic resistance had a synergistic effect on eradication rates. The majority of side effects were mild and none was serious. CONCLUSIONS The 10 day concomitant therapy yielded an eradication rate of nearly 90%. Antibiotic resistance, CYP2C19 polymorphisms and their interactions were closely associated with regimen efficacy.
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Affiliation(s)
- Junbo Hong
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Xu Shu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Dongsheng Liu
- Institute of Digestion, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Yin Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Chuan Xie
- Institute of Digestion, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Yong Xie
- Institute of Digestion, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Kunhe Zhang
- Institute of Digestion, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Anjiang Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Huifang Xiong
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Huilie Zeng
- Department of Statistics of Medical College of Nanchang University, 681 Bayi Road, Nanchang, Jiangxi, P.R. China
| | - Huiqiang Yu
- Department of Statistics of Medical College of Nanchang University, 681 Bayi Road, Nanchang, Jiangxi, P.R. China
| | - Jiuhong Ma
- Digestive Endoscopy Center, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Youxiang Chen
- Digestive Endoscopy Center, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Xuan Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Nonghua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
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17
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Zhou L, Zhang J, Song Z, He L, Li Y, Qian J, Bai P, Xue Y, Wang Y, Lin S. Tailored versus Triple plus Bismuth or Concomitant Therapy as Initial Helicobacter pylori Treatment: A Randomized Trial. Helicobacter 2016; 21:91-9. [PMID: 26104022 DOI: 10.1111/hel.12242] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND With markedly increased antibiotic resistance and unsatisfactory efficacies of common empiric eradication regimens in the mainland of China, tailored therapy may be the best choice to achieve good efficacy. This study compared the eradication rates, safety, and compliance of tailored therapy to those of triple therapy plus bismuth and concomitant therapy in the naïve patients with Helicobacter pylori infection. MATERIALS AND METHODS Between September 2013 and April 2014, 1050 patients with H. pylori infection at three tertiary hospitals were randomly assigned to 10-day treatment with tailored, triple plus bismuth, or concomitant regimens. In tailored therapy, medications were adjusted according to clarithromycin sensitivity and cytochrome P450 isoenzyme 2C19 genotype. The antimicrobial susceptibility testing (E test) was performed. Eradication status was assessed 4-12 weeks after treatment. RESULTS The eradication rate was significantly higher in tailored group than in triple plus bismuth and concomitant groups in both intention-to-treat (88.7 vs 77.4 vs 78.3%, p < .001) and per-protocol (93.3 vs 87.0 vs 87.4%, p = .021) analyses in a setting with high antibiotic resistance (clarithromycin 48.8%, metronidazole 65.7%, and dual resistance 35.3%). Significantly, fewer adverse effects occurred in tailored group than in concomitant group (22.0 vs 31.7%, p = .018). The eradication rates of dual clarithromycin and metronidazole resistance, isolated clarithromycin resistance, isolated metronidazole resistance, and dual susceptible were 78.7, 82.4, 94.8, and 94.4% in triple therapy plus bismuth and 75.9, 87.2, 92.9, and 95.2% in concomitant therapy, respectively. CONCLUSIONS First-line tailored therapy achieves significantly higher eradication rates and fewer side effects, compared to triple therapy plus bismuth and concomitant therapy in a setting with high rates of clarithromycin and metronidazole resistance.
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Affiliation(s)
- Liya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Jianzhong Zhang
- State Key Laboratory for Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Zhiqiang Song
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Lihua He
- State Key Laboratory for Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China
| | - Yanqing Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Shandong, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
| | - Peng Bai
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yan Xue
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Ye Wang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Sanren Lin
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
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18
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van Leeuwen RWF, Peric R, Hussaarts KGAM, Kienhuis E, IJzerman NS, de Bruijn P, van der Leest C, Codrington H, Kloover JS, van der Holt B, Aerts JG, van Gelder T, Mathijssen RHJ. Influence of the Acidic Beverage Cola on the Absorption of Erlotinib in Patients With Non-Small-Cell Lung Cancer. J Clin Oncol 2016; 34:1309-14. [PMID: 26858332 DOI: 10.1200/jco.2015.65.2560] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Erlotinib depends on stomach pH for its bioavailability. When erlotinib is taken concurrently with a proton pump inhibitor (PPI), stomach pH increases, which results in a clinically relevant decrease of erlotinib bioavailability. We hypothesized that this drug-drug interaction is reversed by taking erlotinib with the acidic beverage cola. The effects of cola on erlotinib bioavailability in patients not treated with a PPI were also studied. PATIENTS AND METHODS In this randomized, cross-over, pharmacokinetic study in patients with non-small-cell lung cancer, we studied intrapatient differences in absorption (area under the plasma concentration time curve [AUC0-12h]) after a 7-day period of concomitant treatment with erlotinib, with or without esomeprazole, with either cola or water. At the 7th and 14th day, patients were hospitalized for 1 day for pharmacokinetic sampling. RESULTS Twenty-eight evaluable patients were included in the analysis. In patients treated with erlotinib and esomeprazole with cola, the mean AUC0-12h increased 39% (range, -12% to 136%; P = .004), whereas in patients not treated with the PPI, the mean AUC0-12h was only slightly higher (9%; range, -10% to +30%; P = .03) after erlotinib intake with cola. CONCLUSION Cola intake led to a clinically relevant and statistically significant increase in the bioavailability of erlotinib during esomeprazole treatment. In patients not treated with the PPI, the effects of cola were marginal. These findings can be used to optimize the management of drug-drug interactions between PPIs and erlotinib.
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Affiliation(s)
- Roelof W F van Leeuwen
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands.
| | - Robert Peric
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands
| | - Koen G A M Hussaarts
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands
| | - Emma Kienhuis
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands
| | - Nikki S IJzerman
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands
| | - Peter de Bruijn
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands
| | - Cor van der Leest
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands
| | - Henk Codrington
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands
| | - Jeroen S Kloover
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands
| | - Bronno van der Holt
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands
| | - Joachim G Aerts
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands
| | - Teun van Gelder
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands
| | - Ron H J Mathijssen
- Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands
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Saito Y, Serizawa H, Kato Y, Nakano M, Nakamura M, Saito H, Suzuki H, Kanai T. First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype. World J Gastroenterol 2015; 21:13548-13554. [PMID: 26730167 PMCID: PMC4690185 DOI: 10.3748/wjg.v21.i48.13548] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 09/03/2015] [Accepted: 10/20/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effect of first line esomeprazole (EPZ)-based triple therapy on Helicobacter pylori (H. pylori) eradication.
METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or 13C-urea breath tests were included in this study. The average age of the patients was 57.2 years (male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen (PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry (UMIN000009642).
RESULTS: The H. pylori eradication rates by EPZ-based triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors (PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM (P < 0.05). The serum PG I level and PG I/II ratio were significantly increased after eradication of H. pylori (P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZ-based triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other first-generation PPIs in the Japanese population.
CONCLUSION: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other first-generation PPIs.
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20
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Lima JJ, Franciosi JP. Pharmacogenomic testing: the case for CYP2C19 proton pump inhibitor gene-drug pairs. Pharmacogenomics 2015; 15:1405-16. [PMID: 25303292 DOI: 10.2217/pgs.14.103] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The use of proton pump inhibitors (PPIs) in the treatment of gastroesophageal reflux and related diseases is increasing, especially in the pediatric population. Prolonged use of PPIs has been associated with several adverse effects, including potentially life-threatening gastric and respiratory infections, which are related to dose or to the degree of gastric acid suppression. Genetic variation in the CYP2C19 gene gives rise to poor and extensive metabolizer phenotypes, which influence PPI clearance, efficacy and exposure. A recent paper linked lansoprazole-associated respiratory infections in children with the poor metabolizer phenotype. The case is made for implementing pharmacogenomic testing for the CYP2C19-PPI gene-drug pair and to dose accordingly in order to minimize PPI-associated infections.
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Affiliation(s)
- John J Lima
- Center for Pharmacogenomics & Translational Research, Nemours Children's Clinic, 807 Children's Way, Jacksonville, FL 32207, USA
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21
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Furuta K, Kohata Y, Fujiwara Y, Sugimoto M, Uotani T, Yamade M, Sahara S, Ichikawa H, Furuta T, Nio K, Iwakiri R, Inamori M, Kawamura O, Kusano M, Kato M, Kawami N, Iwakiri K, Takeuchi T, Higuchi K, Aimi M, Naora K, Fujimoto K, Arakawa T, Kinoshita Y. Intra-gastric pH following single oral administrations of rabeprazole and esomeprazole: double-blind cross-over comparison. J Clin Biochem Nutr 2014; 55:178-83. [PMID: 25411523 PMCID: PMC4227829 DOI: 10.3164/jcbn.14-41] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Accepted: 05/14/2014] [Indexed: 01/25/2023] Open
Abstract
Comparisons between the acid inhibitory effects of rabeprazole and esomeprazole after single oral administration with standard doses have not been previously presented. We examined intra-gastric pH after oral administrations of these two proton pump inhibitors using 24-h pH monitoring. Fifty-four normal volunteers not infected by Helicobacter pylori were investigated. Using a cross-over design, we administered 10 mg of rabeprazole or 20 mg of esomeprazole in 27 at 30 min after supper and in the remaining 27 subjects at 15 min before supper, and performed 24-h pH monitoring. Intra-gastric pH data were nearly identical when the proton pump inhibitors were taken after meals. Even if the data were compared in different CYP2C19 genotypes, rabeprazole and esomeprazole did not show the difference. In poor metabolizer, both of the drugs showed stronger acid inhibition. When taken before meals, intra-gastric pH after esomeprazole administration was slightly but not significantly higher than that observed after rabeprazole administration not only in daytime but also in nighttime period. In conclusion, rabeprazole and esomeprazole were similarly effective when administered after a meal.
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Affiliation(s)
- Kenji Furuta
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan
| | - Yukie Kohata
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-5-7 Asahi-cho, Abeno-ku, Osaka 545-8586, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-5-7 Asahi-cho, Abeno-ku, Osaka 545-8586, Japan
| | - Mitsushige Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan
| | - Takahiro Uotani
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan
| | - Mihoko Yamade
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan
| | - Shu Sahara
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan
| | - Hitomi Ichikawa
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan
| | - Kenta Nio
- Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan
| | - Ryuichi Iwakiri
- Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan
| | - Masahiko Inamori
- Gastroenterology Division, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
| | - Osamu Kawamura
- Department of Gastroenterology, Gunma University Hospital, 3-39-15 Showa-cho, Maebashi, Gunma 371-8511, Japan
| | - Motoyasu Kusano
- Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, 3-39-15 Showa-cho, Maebashi, Gunma 371-8511, Japan
| | - Mototsugu Kato
- Division of Endoscopy, Hokkaido University Hospital, Nishi 5-chome, Kita 14-jou, Kita-ku, Sapporo, Hokkaido 060-8648, Japan
| | - Noriyuki Kawami
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
| | - Katsuhiko Iwakiri
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
| | - Toshihisa Takeuchi
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki, Osaka 569-8686, Japan
| | - Kazuhide Higuchi
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki, Osaka 569-8686, Japan
| | - Masahito Aimi
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan
| | - Kohji Naora
- Department of Pharmacy, Shimane University Hospital, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan
| | - Kazuma Fujimoto
- Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan
| | - Tetsuo Arakawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-5-7 Asahi-cho, Abeno-ku, Osaka 545-8586, Japan
| | - Yoshikazu Kinoshita
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan
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Goirand F, Le Ray I, Bardou M. Pharmacokinetic evaluation of esomeprazole for the treatment of gastroesophageal reflux disease. Expert Opin Drug Metab Toxicol 2014; 10:1301-11. [PMID: 25019289 DOI: 10.1517/17425255.2014.939627] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases such as gastroesophageal reflux disease (GERD). They are recommended by the American College of Gastroenterology for healing erosive esophagitis (EO) and as long-term treatment in patients with healed EO. The available PPIs differ somewhat in their pharmacokinetics and clinical properties, but whether these differences are of clinical relevance is a matter of debate. Some safety concerns have been raised with the use of PPIs, mostly an increased incidence of infectious diseases such as community-acquired pneumonia or Clostridium difficile diarrhea. AREAS COVERED This article explores the results of clinical studies on the pharmacokinetics and pharmacodynamics of esomeprazole , as well as on its clinical efficacy to manage patients with GERD. EXPERT OPINION GERD is a public health concern as its worldwide incidence and associated complications are increasing alongside the exponentially increasing problem of obesity. PPIs are the first pharmacological option because of their efficacy and overall positive risk-to-benefit ratio. Improved efficacy with the use of stereospecific isomers of PPIs, such as esomeprazole, has not yet been convincingly demonstrated. Nevertheless, because of individual experience with former treatment, some patients may report better symptom control when treated with a specific PPI rather than with others.
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Affiliation(s)
- Françoise Goirand
- CRI U866, INSERM (Institut National de la Santé et de la Recherche Médicale) , Dijon , France
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Yang JC, Lu CW, Lin CJ. Treatment of Helicobacter pylori infection: current status and future concepts. World J Gastroenterol 2014; 20:5283-93. [PMID: 24833858 PMCID: PMC4017043 DOI: 10.3748/wjg.v20.i18.5283] [Citation(s) in RCA: 145] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 11/28/2013] [Accepted: 01/19/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is highly associated with the occurrence of gastrointestinal diseases, including gastric inflammation, peptic ulcer, gastric cancer, and gastric mucosa-associated lymphoid-tissue lymphoma. Although alternative therapies, including phytomedicines and probiotics, have been used to improve eradication, current treatment still relies on a combination of antimicrobial agents, such as amoxicillin, clarithromycin, metronidazole, and levofloxacin, and antisecretory agents, such as proton pump inhibitors (PPIs). A standard triple therapy consisting of a PPI and two antibiotics (clarithromycin and amoxicillin/metronidazole) is widely used as the first-line regimen for treatment of infection, but the increased resistance of H. pylori to clarithromycin and metronidazole has significantly reduced the eradication rate using this therapy and bismuth-containing therapy or 10-d sequential therapy has therefore been proposed to replace standard triple therapy. Alternatively, levofloxacin-based triple therapy can be used as rescue therapy for H. pylori infection after failure of first-line therapy. The increase in resistance to antibiotics, including levofloxacin, may limit the applicability of such regimens. However, since resistance of H. pylori to amoxicillin is generally low, an optimized high dose dual therapy consisting of a PPI and amoxicillin can be an effective first-line or rescue therapy. In addition, the concomitant use of alternative medicine has the potential to provide additive or synergistic effects against H. pylori infection, though its efficacy needs to be verified in clinical studies.
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Budzyński J, Koziński M, Kłopocka M, Kubica JM, Kubica J. Clinical significance of Helicobacter pylori infection in patients with acute coronary syndromes: an overview of current evidence. Clin Res Cardiol 2014; 103:855-86. [PMID: 24817551 DOI: 10.1007/s00392-014-0720-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Accepted: 04/24/2014] [Indexed: 12/19/2022]
Abstract
Although Helicobacter pylori (Hp) primarily colonizes gastric mucosa, it can occasionally inhabit in atherosclerotic plaques. Both forms of Hp infection may be involved in the pathogenesis of atherosclerosis via activation of a systemic or local inflammatory host reaction and induction of plaque progression and/or instability, possibly leading to coronary syndromes. The association between Hp infection and cardiovascular endpoint prevalence remains uncertain; however, it has been reported in many epidemiological investigations and may be reasonably explained by pathophysiological mechanisms. Besides the inflammatory pathway, Hp infection may trigger acute coronary syndromes by enhanced platelet reactivity and increased risk of gastrointestinal bleeding (type 2 myocardial infarction). The former seems to be predominantly related to the stimulatory effect of Hp infection on von Willebrand factor-binding and P-selectin activation, and the latter results from cytotoxic bacteria properties and aggravation of digestive tract injury related to aspirin or dual antiplatelet therapy. Despite these premises, the role of Hp infection in cardiovascular syndromes should still be recognized as controversial and requiring randomized, controlled trials to evaluate the outcome of Hp eradication in both cardiac and gastroenterological endpoints. Such need is also justified by potential bias of previous studies resulting from (1) using different diagnostic methods for identification of Hp infection, since only a small number of studies required confirmation of active Hp infection; and from (2) common lack of adjustment for important confounders such as socioeconomic status, smoking and effectiveness of eradication therapy, as well as the genetic characteristics of both the host and the bacterium.
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Affiliation(s)
- Jacek Budzyński
- Department of Gastroenterology, Vascular Diseases and Internal Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland,
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Masclee GMC, Sturkenboom MCJM, Kuipers EJ. A Benefit–Risk Assessment of the Use of Proton Pump Inhibitors in the Elderly. Drugs Aging 2014; 31:263-82. [DOI: 10.1007/s40266-014-0166-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Tse SA, Atayee RS, Ma JD, Best BM. Factors affecting carisoprodol metabolism in pain patients using urinary excretion data. J Anal Toxicol 2014; 38:122-8. [PMID: 24488112 DOI: 10.1093/jat/bku002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Carisoprodol is a skeletal muscle relaxant prescribed to treat pain. Carisoprodol is metabolized to meprobamate, an active metabolite with anxiolytic effects, by the genetically polymorphic CYP2C19 enzyme. Concomitant use of CYP2C19 substrates or inhibitors may alter carisoprodol metabolism, with therapeutic and/or toxic implications for effectively treating patients with pain. This was a retrospective analysis of urinary excretion data collected from patients with pain from March 2008 to May 2011. Carisoprodol and meprobamate urine concentrations were measured by liquid chromatography-tandem mass spectrometry, and the metabolic ratio (MR) of meprobamate to carisoprodol concentrations was determined in 14,965 subjects. The MR geometric mean and 95% confidence interval (95% CI) of the young group (105, 95% CI = 99.1-113) were ∼47.4% higher than the middle-aged group (71.9, 95% CI = 70-73.8) and nearly two times higher than the elderly group (54.4, 95% CI = 51.3-57.6). Females had a 20.7% higher MR compared with males. No significant change in the MR was observed with overall CYP2C19 inhibitor or substrate use. However, evaluation of individual inhibitors showed co-administration with esomeprazole or fluoxetine was associated with a 31.8 and 24.6% reduction in MR, respectively, compared with controls (P < 0.05). Omeprazole did not significantly affect the MR. Patient-specific factors such as age, sex and co-medications may be important considerations for effective carisoprodol therapy.
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Affiliation(s)
- Stephanie A Tse
- 1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego (UC San Diego), 9500 Gilman Drive, MC 0719, La Jolla, CA 92093-0719, USA
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Intragastric acidity during the first day following administration of low-dose proton pump inhibitors: a randomized crossover study. Clin Res Hepatol Gastroenterol 2013; 37:296-301. [PMID: 22959094 DOI: 10.1016/j.clinre.2012.07.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Revised: 06/28/2012] [Accepted: 07/04/2012] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Low-dose proton pump inhibitors (PPIs) are often administrated as maintenance therapy for gastroesophageal reflux disease (GERD) and on-demand PPI therapy is a viable option for long-term management of GERD. The aim of this study is to investigate intragastric acidity during the first day following the administration of low-dose PPIs. SUBJECTS AND METHODS The study employed a crossover design. The subjects were 10 healthy volunteers who were administrated lansoprazole 15 mg (orally disintegrating) or rabeprazole 10mg. All subjects underwent pH monitoring with a wireless system during the first day after PPI administration. RESULTS There was no significant difference in the average intragastric pH during the first day of administration of lansoprazole and rabeprazole (3.3±1.1 vs. 3.2±0.7, paired t test), although the pH was significantly higher with both drugs as compared with the baseline (1.8±0.4, P<0.01). The pH 4 holding time ratio during the first day showed no significant difference between lansoprazole and rabeprazole (35.2±22.4% vs. 34.3±15.0%), and was also significantly higher than at baseline (0.35±1.73%, P<0.01). The two PPIs differed with respect to the peak of the pH 4 holding time ratio. CONCLUSIONS Lansoprazole 15 mg and rabeprazole 10 mg showed sufficient inhibition of intragastric acidity during the first day after PPI administration and the effects did not differ between drugs, although there was a difference in their time at which the peak effects were reached.
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Liu WZ, Xie Y, Cheng H, Lu NH, Hu FL, Zhang WD, Zhou LY, Chen Y, Zeng ZR, Wang CW, Xiao SD, Pan GZ, Hu PJ. Fourth Chinese National Consensus Report on the management of Helicobacter pylori infection. J Dig Dis 2013; 14:211-21. [PMID: 23302262 DOI: 10.1111/1751-2980.12034] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
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- Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Individualized therapy for gastroesophageal reflux disease: potential impact of pharmacogenetic testing based on CYP2C19. Mol Diagn Ther 2012; 16:223-34. [PMID: 22873740 DOI: 10.1007/bf03262211] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The main therapeutic agent for gastroesophageal reflux disease (GERD) is a proton pump inhibitor (PPI). Plasma levels and the acid inhibitory effect of PPIs depend on the activity of cytochrome P450 (CYP) 2C19, which is polymorphic. Genotypes of CYP2C19 are classified into three groups: rapid metabolizers (RMs: *1/*1), intermediate metabolizers (IMs: *1/*X), and poor metabolizers (PMs: *X/*X), where *1 and X represent the wild type and the mutant allele, respectively. RMs include ultra-rapid metabolizers, who possess the CYP2C19*17 allele. The pharmacokinetics and pharmacodynamics of PPIs differ among different CYP2C19 genotype groups. Plasma PPI levels and intragastric pH values during PPI treatment are lowest in the RM group, intermediate in the IM group, and highest in the PM group. These CYP2C19-genotype-dependent differences in the pharmacokinetics and pharmacodynamics of PPIs influence the healing and recurrence of GERD during PPI treatment, suggesting the need for CYP2C19 genotype-based tailored therapy for GERD. CYP2C19 pharmacogenetics should be taken into consideration for the personalization of PPI-based therapy. However, the clinical usefulness of CYP2C19 genotype testing in GERD therapy should be verified in clinical studies.
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Furuta T, Sugimoto M, Shirai N. Individualized therapy for gastroesophageal reflux disease: potential impact of pharmacogenetic testing based on CYP2C19. Mol Diagn Ther 2012. [PMID: 22873740 DOI: 10.2165/11634960-000000000-00000] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The main therapeutic agent for gastroesophageal reflux disease (GERD) is a proton pump inhibitor (PPI). Plasma levels and the acid inhibitory effect of PPIs depend on the activity of cytochrome P450 (CYP) 2C19, which is polymorphic. Genotypes of CYP2C19 are classified into three groups: rapid metabolizers (RMs: *1/*1), intermediate metabolizers (IMs: *1/*X), and poor metabolizers (PMs: *X/*X), where *1 and X represent the wild type and the mutant allele, respectively. RMs include ultra-rapid metabolizers, who possess the CYP2C19*17 allele. The pharmacokinetics and pharmacodynamics of PPIs differ among different CYP2C19 genotype groups. Plasma PPI levels and intragastric pH values during PPI treatment are lowest in the RM group, intermediate in the IM group, and highest in the PM group. These CYP2C19-genotype-dependent differences in the pharmacokinetics and pharmacodynamics of PPIs influence the healing and recurrence of GERD during PPI treatment, suggesting the need for CYP2C19 genotype-based tailored therapy for GERD. CYP2C19 pharmacogenetics should be taken into consideration for the personalization of PPI-based therapy. However, the clinical usefulness of CYP2C19 genotype testing in GERD therapy should be verified in clinical studies.
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Affiliation(s)
- Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.
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