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Berrou I. Prescribing metformin for patients with non-diabetic hyperglycaemia or type 2 diabetes. Nurs Stand 2025:e12437. [PMID: 40159768 DOI: 10.7748/ns.2025.e12437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/21/2024] [Indexed: 04/02/2025]
Abstract
Metformin hydrochloride is a prescription-only oral medicine that is frequently encountered in clinical practice. It is recommended in most diabetes mellitus guidelines as a first-line treatment option for some people with non-diabetic hyperglycaemia and most people with type 2 diabetes. Metformin is usually well-tolerated and safe if prescribed appropriately. However, despite its common use, there are several important factors that healthcare practitioners need to consider when intending to prescribe metformin and once it has been initiated. This article discusses the use of metformin in non-diabetic hyperglycaemia and type 2 diabetes, and explores how healthcare practitioners can ensure safe prescribing of this medicine.
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Affiliation(s)
- Ilhem Berrou
- University of the West of England, Bristol, England
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2
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Boadu AA, Yeboah-Manu M, Osei-Wusu S, Yeboah-Manu D. Tuberculosis and diabetes mellitus: The complexity of the comorbid interactions. Int J Infect Dis 2024; 146:107140. [PMID: 38885832 DOI: 10.1016/j.ijid.2024.107140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 05/31/2024] [Accepted: 06/13/2024] [Indexed: 06/20/2024] Open
Abstract
The double burden of tuberculosis (TB) and diabetes mellitus (DM) represents a major public health challenge that demands urgent and integrated approaches. The interplay between these two chronic conditions presents unique clinical and public health management challenges, as well as social and economic implications. We explored the bidirectional relationship between TB and DM, emphasizing how DM increases susceptibility to TB and complicates its management, while TB may exacerbate glycemic control in diabetic patients. This review underscores the challenges associated with the management of both diseases, obstacles in screening TB patients for DM and TB preventive therapy for DM since inadequate glycemic control can impact treatment outcomes. Several studies have investigated the disease interplay; however, the results have been equivocal, and this may be exerting negative impacts on the disease prevention and treatment. TB-diabetes comorbidity has been linked to poor treatment outcomes whereas TB prevention in people with DM at present is a dilemma. In addition to highlighting how urgent it is to address this comorbidity, this review offers a road map for better prevention, treatment, and control of several factors underlying the TB-diabetes syndemic interaction.
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Affiliation(s)
- Augustine Asare Boadu
- Department of Bacteriology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon-Accra, Ghana; Department of Biomedical Sciences, School of Allied Health Sciences, University of Cape Coast, Cape Coast, Ghana
| | | | - Stephen Osei-Wusu
- Department of Bacteriology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon-Accra, Ghana
| | - Dorothy Yeboah-Manu
- Department of Bacteriology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon-Accra, Ghana.
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Cluver CA, Bergman L, Imberg H, Mol BW, Hall D, Bekker A, Gordon A, Brownfoot F, Kaitu'u-Lino TJ, Walker SP, Tong S. Does metformin prolong pregnancy in preterm pre-eclampsia? A study protocol for a South African, hospital-based double-blind, randomised, placebo-controlled trial. BMJ Open 2024; 14:e082880. [PMID: 38890136 PMCID: PMC11191812 DOI: 10.1136/bmjopen-2023-082880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 05/21/2024] [Indexed: 06/20/2024] Open
Abstract
INTRODUCTION Preterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week in pregnant women undergoing expectant management (7.6 days, geometric mean ratio 1.39, 95% CI 0.99 to 1.95; p=0.057). These findings should be confirmed with a larger sample size, and we need to know if such a prolongation improves neonatal outcome. Here, we describe the protocol for such a follow-up trial. METHODS The PI 3 trial is a phase III, intention-to-treat, double-blind, placebo-controlled randomised clinical trial to assess if metformin XR can prolong gestation and improve neonatal outcomes in women undergoing expectant management for preterm pre-eclampsia. We will recruit women who are between 26+0 and 31+6 weeks pregnant. Women will be randomised to receive either 3 g metformin XR or an identical placebo in divided daily doses. The primary outcome is prolongation of pregnancy. Secondary outcomes are neonatal birth weight and length of neonatal care admission (an indicator of neonatal health at birth). All other outcomes will be exploratory. We will record tolerability and adverse events. We plan a sample size of 500 participants to be powered for the primary and secondary outcomes. ETHICS AND DISSEMINATION PI 3 has ethical approval (Health Research Ethics Committee 2, Stellenbosch University, Protocol number M21/03/007, Project ID 21639, Federal Wide Assurance Number 00001372, Institutional Review Board Number IRB0005239), and is registered with the Pan African Clinical Trial Registry (PACTR202104532026017) and the South African Medicine Control Council (20211211). Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER PACTR202104532026017).
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Affiliation(s)
- Catherine Anne Cluver
- Department of Obstetrics and Gynaecology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa
- Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, Melbourne University, Heidelberg, Victoria, Australia
- Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
| | - Lina Bergman
- Department of Obstetrics and Gynaecology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa
- Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Ben W Mol
- Department of Obstetrics and Gynaecology, Monash Medical School, Monash University, Melbourne, Victoria, Australia
| | - David Hall
- Department of Obstetrics and Gynaecology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa
| | - Adrie Bekker
- Department of Paediatrics, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa
| | - Adrienne Gordon
- Discipline of Obstetrics, Gynaecology and Neonatology, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Fiona Brownfoot
- Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, Melbourne University, Heidelberg, Victoria, Australia
- Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
| | - Tu'uhevaha J Kaitu'u-Lino
- Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, Melbourne University, Heidelberg, Victoria, Australia
- Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
| | - Susan P Walker
- Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, Melbourne University, Heidelberg, Victoria, Australia
- Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
| | - Stephen Tong
- Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, Melbourne University, Heidelberg, Victoria, Australia
- Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
- Translational Obstetrics Group and Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Melbourne, Victoria, Australia
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Kumar AKH, Kadam A, Karunaianantham R, Tamizhselvan M, Padmapriyadarsini C, Mohan A, Jeyadeepa B, Radhakrishnan A, Singh UB, Bapat S, Mane A, Kumar P, Mamulwar M, Bhavani PK, Haribabu H, Rath N, Guleria R, Khan AM, Menon J. Effect of Metformin on Plasma Exposure of Rifampicin, Isoniazid, and Pyrazinamide in Patients on Treatment for Pulmonary Tuberculosis. Ther Drug Monit 2024; 46:370-375. [PMID: 38019456 PMCID: PMC11078288 DOI: 10.1097/ftd.0000000000001149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Accepted: 08/08/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND To evaluate the effect of metformin on the plasma levels of rifampicin, isoniazid, and pyrazinamide in patients with drug-sensitive pulmonary tuberculosis being treated with first-line antituberculosis treatment (ATT) and to assess the influence of gene polymorphisms on the metabolic pathway of metformin and plasma levels of antitubercular drugs. METHODS Nondiabetic adults aged 18-60 years with pulmonary tuberculosis were randomized to either the standard ATT (ATT group) or ATT plus metformin (METRIF group) groups in a phase IIB clinical trial. An intensive pharmacokinetic study with blood collection at 0 hour (predosing), followed by 1, 2, 4, 6, 8, and 12 hours after dosing was conducted during the first month of treatment in a subset of 60 study participants after a minimum of 14 doses. Plasma concentrations of rifampicin, isoniazid, pyrazinamide, and metformin were measured by high-performance liquid chromatography using validated methods, and pharmacokinetic parameters and OCT1 and MATE1 gene polymorphisms were compared between the groups. RESULTS Significant increases in the clearance of rifampicin, isoniazid, and pyrazinamide were observed in patients in the METRIF group (n = 29) compared with those in the ATT group (n = 31). The AA genotypes of the single-nucleotide polymorphism of rs2289669 ( MATE1 ) in the METRIF group showed a significantly decreased area under the concentration-time curve to the last observation point and increased clearance of rifampicin. CONCLUSIONS Metformin altered rifampicin and isoniazid plasma concentrations in patients receiving antituberculosis treatment for pulmonary tuberculosis with little effect on sputum conversion at the end of treatment. Studies with larger sample sizes are needed to understand host drug-drug interactions.
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Affiliation(s)
| | | | | | | | | | - Anant Mohan
- All India Institute of Medical Sciences, New Delhi
| | - B. Jeyadeepa
- ICMR-National Institute for Research in Tuberculosis, Chennai
| | | | | | | | - Aarti Mane
- ICMR-National AIDS Research Institute, Pune
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Al-Bari MAA, Peake N, Eid N. Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges. World J Diabetes 2024; 15:853-866. [PMID: 38766427 PMCID: PMC11099355 DOI: 10.4239/wjd.v15.i5.853] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 02/08/2024] [Accepted: 03/21/2024] [Indexed: 05/10/2024] Open
Abstract
Tuberculosis (TB) remains a leading cause of death among infectious diseases, particularly in poor countries. Viral infections, multidrug-resistant and ex-tensively drug-resistant TB strains, as well as the coexistence of chronic illnesses such as diabetes mellitus (DM) greatly aggravate TB morbidity and mortality. DM [particularly type 2 DM (T2DM)] and TB have converged making their control even more challenging. Two contemporary global epidemics, TB-DM behaves like a syndemic, a synergistic confluence of two highly prevalent diseases. T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive treatment. Since a bidirectional relationship exists between TB and DM, it is necessary to concurrently treat both, and promote recommendations for the joint management of both diseases. There are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure, and reinfection. In addition, autophagy may play a role in these comorbidities. Therefore, the TB-DM comorbidities present several health challenges, requiring a focus on multidisciplinary collaboration and integrated strategies, to effectively deal with this double burden. To effectively manage the comorbidity, further screening in affected countries, more suitable drugs, and better treatment strategies are required.
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Affiliation(s)
| | - Nicholas Peake
- Biosciences and Chemistry and Biomolecular Research Centre, Sheffield Hallam University, Sheffield S1 1WB, United Kingdom
| | - Nabil Eid
- Department of Anatomy, Division of Human Biology, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
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Torunoglu ST, Zajda A, Tampio J, Markowicz-Piasecka M, Huttunen KM. Metformin derivatives - Researchers' friends or foes? Biochem Pharmacol 2023; 215:115743. [PMID: 37591450 DOI: 10.1016/j.bcp.2023.115743] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 08/09/2023] [Accepted: 08/09/2023] [Indexed: 08/19/2023]
Abstract
Metformin has been used for ages to treat diabetes mellitus due to its safety profile and low cost. However, metformin has variable pharmacokinetics in patients, and due to its poor oral absorption, the therapeutic doses are relatively high, causing unpleasant gastrointestinal adverse effects. Therefore, novel derivatives of metformin have been synthesized during the past decades. Particularly, after the mid-2000 s, when organic cation transporters were identified as the main metformin carriers, metformin derivatives have been under intensive investigation. Nevertheless, due to the biguanide structure, derivatives of metformin have been challenging to synthesize. Moreover, the mechanisms of metformin's action are not fully understood to date, and since it has multifunctional properties, the interests have switched to re-purposing for other diseases. Indeed, metformin derivatives have been demonstrated in many cases to be more effective than metformin itself and have the potential to be used in different diseases, including several types of cancers and neurodegenerative diseases. On the other hand, the pleiotropic nature of metformin and its derivatives can also create challenges. Not all properties are fit for all diseases. In this review, the history of the development of metformin-like compounds is summarized, and insights into their potential for future drug discovery are discussed.
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Affiliation(s)
- Sema Tuna Torunoglu
- School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
| | - Agnieszka Zajda
- Laboratory of Bioanalysis, Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, ul. Muszyńskiego 1, 90-151 Lodz, Poland
| | - Janne Tampio
- School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland
| | | | - Kristiina M Huttunen
- School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
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Mary Rebecca Y, Sudha V, Bharathiraja T, Kannan T, Lavanya J, Hemanth Kumar AK. Urinary excretion of metformin in diabetic patients with and without tuberculosis. Indian J Tuberc 2023; 70:37-41. [PMID: 36740315 DOI: 10.1016/j.ijtb.2022.03.004] [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: 10/08/2021] [Accepted: 03/03/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Patients with concurrent diabetes mellitus (DM) and tuberculosis (TB) pose an increased risk of treatment failure in TB and management of DM is complicated. Anti-diabetic and anti-TB drugs may interact with on another other when co-administered. The role of anti-TB drugs on the excretion of metformin in urine has not been studied. Therefore, we carried out a study in DM patients with and without TB to compare the percentage of metformin excreted in urine. METHODS A total of 52 DMTB and 17 DM patients were recruited in this study from the Chennai Corporation Centres. DM and DM - TB patients were administered the prescribed anti-TB and anti-diabetic drugs (metformin (MET), glipizide (GLP),glimepiride (GLM),glibenclamide (GLB),rifampicin (RMP),isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB). DM and DMTB patients received metformin (MET) alone and in combination with sulphonylureas as diabetic drugs. The urine samples were collected from 0 to 8 hours after drug administration. Urine MET excreted in DM and DMTB patients were estimated by high performance liquid chromatography (HPLC) and percent dose was calculated. RESULTS The percent dose of MET excreted in urine in DMTB patients was significantly higher when compared to DM patients. There is significant difference in the percent dose of MET excreted among DM patients with and without sulphonylureas, values being 23.3 and 17.7% respectively (p = 0.044). CONCLUSION This is the first study to report on the percent dose of MET excretion in urine in patients with DM and DMTB receiving MET along with anti-TB drugs.
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Affiliation(s)
- Y Mary Rebecca
- ICMR-National Institute for Research in Tuberculosis, Chennai, India
| | - Vilvamani Sudha
- ICMR-National Institute for Research in Tuberculosis, Chennai, India
| | | | | | - J Lavanya
- Greater Chennai Corporation, Chennai, India
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Nies AT, Schaeffeler E, Schwab M. Hepatic solute carrier transporters and drug therapy: Regulation of expression and impact of genetic variation. Pharmacol Ther 2022; 238:108268. [DOI: 10.1016/j.pharmthera.2022.108268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 07/25/2022] [Accepted: 08/15/2022] [Indexed: 11/30/2022]
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Vakili-Ghartavol R, Mehrabian A, Mirzavi F, Rezayat SM, Mashreghi M, Farhoudi L, Kharrazi S, Sadri K, Jaafari MR. Docetaxel in combination with metformin enhances antitumour efficacy in metastatic breast carcinoma models: a promising cancer targeting based on PEGylated liposomes. J Pharm Pharmacol 2022; 74:1307-1319. [PMID: 35833585 DOI: 10.1093/jpp/rgac048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 06/14/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Metformin has been shown to kill cancer stem-like cells in genetically various types of breast carcinoma. With the aim to simultaneously eradicate the bulk population of tumour cells and the rare population of cancer stem-like cells in breast cancer tissues, we used the combination chemotherapy of docetaxel (DTX) with metformin (MET). Furthermore, we introduce an active loading method based on ammonium sulphate 250 mM (SA) for encapsulating docetaxel into liposomes. METHODS Docetaxel and metformin encapsulated into PEGylated liposomes with two different methods based on remote or passive loading methods, respectively. The size and surface charge of the liposomes were characterized. DTX content in the nanoliposomes was measured by the high-performance liquid chromatography method. The drug release profiles were evaluated in phosphate-buffered dextrose 5% with the pH of 6.5 and 7.4. We examined the antitumour activity of Taxotere (TAX), and liposomal formulation of DTX and MET as a monotherapy or combination therapy. The biodistribution of liposomes was also investigated using 99mTc hexamethyl propylene amine oxime method in BALB/c mice bearing 4T1 breast carcinoma tumours. KEY FINDINGS The final formulations were prepared according to the best physicochemical characteristics which were HSPC/mPEG2000-DSPE/Chol (DTX liposomes) and HSPC/DPPG/mPEG2000-DSPE/Chol (MET liposomes), at molar ratios of 85/5/10 and (55/5/5/35), respectively. In vivo experiments showed that when free or liposomal metformin used in combination with liposomal docetaxel, they prolonged median survival time (MST) from 31 in the control group to 46 days, which demonstrates their promising effects on the survival of the 4T1 breast carcinoma mice models. Moreover, combination therapies could significantly increase life span in comparison with phosphate-buffered saline (PBS) and Taxotere groups at the same dose. Furthermore, in the combination therapy study, treatment with DTX liposomes prepared by ammonium sulphate 250 mM buffer alone resulted in similar therapeutic efficacy to combination therapy. The biodistribution study exhibited significant accumulation of DTX liposomes in the tumours due to the Enhanced Permeability and Retention effect. CONCLUSIONS This study also showed that metformin-based combinatorial chemotherapies have superior efficacy versus their corresponding monotherapy counterparts at same doses. The findings confirm that liposomes based on ammonium sulphate 250 mM could be as a promising formulation for efficient DTX delivering and cancer targeting and therefore merit further investigations.
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Affiliation(s)
- Roghayyeh Vakili-Ghartavol
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Amin Mehrabian
- Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farshad Mirzavi
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Seyed Mahdi Rezayat
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Mashreghi
- Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Leila Farhoudi
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sharmin Kharrazi
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Kayvan Sadri
- Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahmoud Reza Jaafari
- Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.,Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
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Dauki AM, Hsueh C, Cherala G, Othman AA. Oral Glucose Tolerance Test: An Informative Endpoint or an Added Burden in Metformin Drug-Drug Interaction Studies? Clin Pharmacol Ther 2022; 112:453-455. [PMID: 35687738 PMCID: PMC9540494 DOI: 10.1002/cpt.2650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 04/30/2022] [Indexed: 11/25/2022]
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Alffenaar JWC, Stocker SL, Forsman LD, Garcia-Prats A, Heysell SK, Aarnoutse RE, Akkerman OW, Aleksa A, van Altena R, de Oñata WA, Bhavani PK, Van't Boveneind-Vrubleuskaya N, Carvalho ACC, Centis R, Chakaya JM, Cirillo DM, Cho JG, D Ambrosio L, Dalcolmo MP, Denti P, Dheda K, Fox GJ, Hesseling AC, Kim HY, Köser CU, Marais BJ, Margineanu I, Märtson AG, Torrico MM, Nataprawira HM, Ong CWM, Otto-Knapp R, Peloquin CA, Silva DR, Ruslami R, Santoso P, Savic RM, Singla R, Svensson EM, Skrahina A, van Soolingen D, Srivastava S, Tadolini M, Tiberi S, Thomas TA, Udwadia ZF, Vu DH, Zhang W, Mpagama SG, Schön T, Migliori GB. Clinical standards for the dosing and management of TB drugs. Int J Tuberc Lung Dis 2022; 26:483-499. [PMID: 35650702 PMCID: PMC9165737 DOI: 10.5588/ijtld.22.0188] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 04/04/2022] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.
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Affiliation(s)
- J W C Alffenaar
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia, School of Pharmacy, The University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia, Westmead Hospital, Sydney, NSW, Australia
| | - S L Stocker
- School of Pharmacy, The University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia, Department of Clinical Pharmacology and Toxicology, St Vincent´s Hospital, Sydney, NSW, Australia, St Vincent´s Clinical Campus, University of NSW, Kensington, NSW, Australia
| | - L Davies Forsman
- Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Solna, Sweden, Department of Infectious Diseases Karolinska University Hospital, Solna, Sweden
| | - A Garcia-Prats
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg, South Africa, Department of Pediatrics, University of Wisconsin, Madison, WI
| | - S K Heysell
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA
| | - R E Aarnoutse
- Department of Pharmacy, Radboud Institute for Health Sciences & Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - O W Akkerman
- University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands, University of Groningen, University Medical Center Groningen, Tuberculosis Center Beatrixoord, Haren, The Netherlands
| | - A Aleksa
- Educational Institution "Grodno State Medical University", Grodno, Belarus
| | - R van Altena
- Asian Harm Reduction Network (AHRN) and Medical Action Myanmar (MAM) in Yangon, Myanmar
| | - W Arrazola de Oñata
- Belgian Scientific Institute for Public Health (Belgian Lung and Tuberculosis Association), Brussels, Belgium
| | - P K Bhavani
- Indian Council of Medical Research-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai, India
| | - N Van't Boveneind-Vrubleuskaya
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, Department of Public Health TB Control, Metropolitan Public Health Services, The Hague, The Netherlands
| | - A C C Carvalho
- Laboratório de Inovações em Terapias, Ensino e Bioprodutos (LITEB), Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - R Centis
- Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Tradate, Italy
| | - J M Chakaya
- Department of Medicine, Therapeutics and Dermatology, Kenyatta University, Nairobi, Kenya, Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
| | - D M Cirillo
- Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - J G Cho
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia, Westmead Hospital, Sydney, NSW, Australia, Parramatta Chest Clinic, Parramatta, NSW, Australia
| | - L D Ambrosio
- Public Health Consulting Group, Lugano, Switzerland
| | - M P Dalcolmo
- Reference Center Hélio Fraga, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
| | - P Denti
- Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - K Dheda
- Centre for Lung Infection and Immunity, Department of Medicine, Division of Pulmonology and UCT Lung Institute, University of Cape Town, Cape Town, South Africa, University of Cape Town Lung Institute & South African MRC Centre for the Study of Antimicrobial Resistance, Cape Town, South Africa, Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK
| | - G J Fox
- Faculty of Medicine and Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia, Woolcock Institute of Medical Research, Glebe, NSW, Australia
| | - A C Hesseling
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg, South Africa
| | - H Y Kim
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia, School of Pharmacy, The University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia, Westmead Hospital, Sydney, NSW, Australia
| | - C U Köser
- Department of Genetics, University of Cambridge, Cambridge, UK
| | - B J Marais
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia, Department of Infectious Diseases and Microbiology, The Children´s Hospital at Westmead, Westmead, NSW, Australia
| | - I Margineanu
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - A G Märtson
- Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - M Munoz Torrico
- Clínica de Tuberculosis, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, Mexico
| | - H M Nataprawira
- Division of Paediatric Respirology, Department of Child Health, Faculty of Medicine, Universitas Padjadjaran, Hasan Sadikin Hospital, Bandung, Indonesia
| | - C W M Ong
- Infectious Disease Translational Research Programme, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Institute for Health Innovation & Technology (iHealthtech), National University of Singapore, Singapore, Division of Infectious Diseases, Department of Medicine, National University Hospital, Singapore
| | - R Otto-Knapp
- German Central Committee against Tuberculosis (DZK), Berlin, Germany
| | - C A Peloquin
- Infectious Disease Pharmacokinetics Laboratory, Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA
| | - D R Silva
- Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - R Ruslami
- TB/HIV Research Centre, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia, Department of Biomedical Sciences, Division of Pharmacology and Therapy, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - P Santoso
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung, Indonesia
| | - R M Savic
- Department of Bioengineering and Therapeutic Sciences, Division of Pulmonary and Critical Care Medicine, Schools of Pharmacy and Medicine, University of California San Francisco, San Francisco, CA, USA
| | - R Singla
- Department of TB & Respiratory Diseases, National Institute of TB & Respiratory Diseases, New Delhi, India
| | - E M Svensson
- Department of Pharmacy, Radboud Institute for Health Sciences & Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands, Department of Pharmacy, Uppsala University, Uppsala, Sweden
| | - A Skrahina
- The Republican Research and Practical Centre for Pulmonology and TB, Minsk, Belarus
| | - D van Soolingen
- National Institute for Public Health and the Environment, TB Reference Laboratory (RIVM), Bilthoven, The Netherlands
| | - S Srivastava
- Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, TX, USA
| | - M Tadolini
- Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - S Tiberi
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - T A Thomas
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA
| | - Z F Udwadia
- P. D. Hinduja National Hospital and Medical Research Centre, Mumbai, India
| | - D H Vu
- National Drug Information and Adverse Drug Reaction Monitoring Centre, Hanoi University of Pharmacy, Hanoi, Vietnam
| | - W Zhang
- Department of Infectious Diseases, National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People´s Republic of China
| | - S G Mpagama
- Kilimanjaro Christian Medical University College, Moshi, United Republic of Tanzania, Kibong´oto Infectious Diseases Hospital, Sanya Juu, Siha, Kilimanjaro, United Republic of Tanzania
| | - T Schön
- Department of Infectious Diseases, Linköping University Hospital, Linköping, Sweden, Institute of Biomedical and Clinical Sciences, Division of Infection and Inflammation, Linköping University, Linköping, Sweden, Department of Infectious Diseases, Kalmar County Hospital, Kalmar, Linköping University, Linköping, Sweden
| | - G B Migliori
- Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Tradate, Italy
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Cáceres G, Calderon R, Ugarte-Gil C. Tuberculosis and comorbidities: treatment challenges in patients with comorbid diabetes mellitus and depression. Ther Adv Infect Dis 2022; 9:20499361221095831. [PMID: 35646347 PMCID: PMC9130847 DOI: 10.1177/20499361221095831] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Accepted: 04/03/2022] [Indexed: 11/23/2022] Open
Abstract
Tuberculosis is one of the leading causes of death worldwide, primarily affecting
low- and middle income countries and individuals with limited-resources within
fractured health care systems. Unfortunately, the COVID-19 pandemic has only
served to aggravate the already existing diagnostic gap, decreasing the number
of people who get diagnosed and thereby complete successful treatment. In
addition to this, comorbidities act as an external component that when added to
the TB management equation, renders it even more complex. Among the various
comorbidities that interact with TB disease, diabetes mellitus and depression
are two of the most prevalent among non-communicable diseases within the TB
population and merits a thoughtful consideration when the healthcare system
provides care for them. TB patients with diabetes mellitus (TB-DM) or depression
both have an increased risk of mortality, relapse and recurrence. Both of these
diseases when in presence of TB present a ‘vicious-circle-like’ mechanism,
meaning that the effect of each disease can negatively add up, in a synergistic
manner, complicating the patient’s health state. Among TB-DM patients, high
glucose blood levels can decrease the effectiveness of anti-tuberculosis drugs;
however, higher doses of anti-tuberculous drugs could potentially decrease the
effects of DM drugs. Among the TB-depression patients, not only do we have the
adherence to treatment problems, but depression itself can biologically shift
the immunological profile responsible for TB containment, and the other way
around, TB itself can alter the hormonal balance of several neurotransmitters
responsible for depression. In this paper, we review these and other important
aspects such as the pharmacological interactions found in the treatment of TB-DM
and TB-depression patients and the implication on TB care and pharmacological
considerations.
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Affiliation(s)
- Guillermo Cáceres
- Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - Rodrigo Calderon
- Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - Cesar Ugarte-Gil
- Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430-San Martin de Porres, Lima, Perú
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13
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Hegazy WAH, Rajab AAH, Abu Lila AS, Abbas HA. Anti-diabetics and antimicrobials: Harmony of mutual interplay. World J Diabetes 2021; 12:1832-1855. [PMID: 34888011 PMCID: PMC8613656 DOI: 10.4239/wjd.v12.i11.1832] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/26/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetes is one of the four major non-communicable diseases, and appointed by the world health organization as the seventh leading cause of death worldwide. The scientists have turned over every rock in the corners of medical sciences in order to come up with better understanding and hence more effective treatments of diabetes. The continuous research on the subject has elucidated the role of immune disorders and inflammation as definitive factors in the trajectory of diabetes, assuring that blood glucose adjustments would result in a relief in the systemic stress leading to minimizing inflammation. On a parallel basis, microbial infections usually take advantage of immunity disorders and propagate creating a pro-inflammatory environment, all of which can be reversed by antimicrobial treatment. Standing at the crossroads between diabetes, immunity and infection, we aim in this review at projecting the interplay between immunity and diabetes, shedding the light on the overlapping playgrounds for the activity of some antimicrobial and anti-diabetic agents. Furthermore, we focused on the anti-diabetic drugs that can confer antimicrobial or anti-virulence activities.
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Affiliation(s)
- Wael A H Hegazy
- Department of Microbiology and Immunology, Zagazig University, Zagzig 44519, Egypt
| | - Azza A H Rajab
- Department of Microbiology and Immunology, Zagazig University, Zagzig 44519, Egypt
| | - Amr S Abu Lila
- Department of Pharmaceutics, Zagazig University, Faculty of Pharmacy, Zagzig 44519, Egypt
- Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia
| | - Hisham A Abbas
- Department of Microbiology and Immunology, Zagazig University, Zagzig 44519, Egypt
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14
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A Whole-Body Physiologically Based Pharmacokinetic Model Characterizing Interplay of OCTs and MATEs in Intestine, Liver and Kidney to Predict Drug-Drug Interactions of Metformin with Perpetrators. Pharmaceutics 2021; 13:pharmaceutics13050698. [PMID: 34064886 PMCID: PMC8151202 DOI: 10.3390/pharmaceutics13050698] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 04/30/2021] [Accepted: 05/07/2021] [Indexed: 12/27/2022] Open
Abstract
Transmembrane transport of metformin is highly controlled by transporters including organic cation transporters (OCTs), plasma membrane monoamine transporter (PMAT), and multidrug/toxin extrusions (MATEs). Hepatic OCT1, intestinal OCT3, renal OCT2 on tubule basolateral membrane, and MATE1/2-K on tubule apical membrane coordinately work to control metformin disposition. Drug–drug interactions (DDIs) of metformin occur when co-administrated with perpetrators via inhibiting OCTs or MATEs. We aimed to develop a whole-body physiologically based pharmacokinetic (PBPK) model characterizing interplay of OCTs and MATEs in the intestine, liver, and kidney to predict metformin DDIs with cimetidine, pyrimethamine, trimethoprim, ondansetron, rabeprazole, and verapamil. Simulations showed that co-administration of perpetrators increased plasma exposures to metformin, which were consistent with clinic observations. Sensitivity analysis demonstrated that contributions of the tested factors to metformin DDI with cimetidine are gastrointestinal transit rate > inhibition of renal OCT2 ≈ inhibition of renal MATEs > inhibition of intestinal OCT3 > intestinal pH > inhibition of hepatic OCT1. Individual contributions of transporters to metformin disposition are renal OCT2 ≈ renal MATEs > intestinal OCT3 > hepatic OCT1 > intestinal PMAT. In conclusion, DDIs of metformin with perpetrators are attributed to integrated effects of inhibitions of these transporters.
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15
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van Crevel R, Critchley JA. The Interaction of Diabetes and Tuberculosis: Translating Research to Policy and Practice. Trop Med Infect Dis 2021; 6:tropicalmed6010008. [PMID: 33435609 PMCID: PMC7838867 DOI: 10.3390/tropicalmed6010008] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 12/23/2020] [Accepted: 12/31/2020] [Indexed: 12/17/2022] Open
Abstract
Diabetes Mellitus increases the risk of developing Tuberculosis (TB) disease by about three times; it also doubles the risk of death during TB treatment and other poor TB treatment outcomes. Diabetes may increase the risk of latent infection with Mycobacterium tuberculosis (LTBI), but the magnitude of this effect is less clear. Whilst this syndemic has received considerable attention, most of the published research has focussed on screening for undiagnosed diabetes in TB patients or observational follow-up of TB treatment outcomes by diabetes status. There are thus substantial research and policy gaps, particularly with regard to prevention of TB disease in people with diabetes and management of patients with TB-diabetes, both during TB treatment and after successful completion of TB treatment, when they likely remain at high risk of TB recurrence, mortality from TB and cardiovascular disease. Potential strategies to prevent development of TB disease might include targeted vaccination programmes, screening for LTBI and preventive therapy among diabetes patients or, perhaps ideally, improved diabetes management and prevention. The cost-effectiveness of each of these, and in particular how each strategy might compare with targeted TB prevention among other population groups at higher risk of developing TB disease, is also unknown. Despite research gaps, clinicians urgently need practical management advice and more research evidence on the choice and dose of different anti-diabetes medication and effective medical therapies to reduce cardiovascular risks (statins, anti-hypertensives and aspirin). Substantial health system strengthening and integration may be needed to prevent these at risk patients being lost to care at the end of TB treatment.
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Affiliation(s)
- Reinout van Crevel
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6500HB Nijmegen, The Netherlands
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LG, UK
- Correspondence:
| | - Julia A. Critchley
- Population Health Research Institute, St George’s, University of London, London SW17 ORE, UK;
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16
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Mtabho CM, Semvua HH, van den Boogaard J, Irongo CF, Boeree MJ, Colbers A, Burger DM, van Crevel R, van der Ven AJAM, Kibiki GS, Tostmann A, Aarnoutse RE. Effect of diabetes mellitus on TB drug concentrations in Tanzanian patients. J Antimicrob Chemother 2020; 74:3537-3545. [PMID: 31651031 PMCID: PMC7183353 DOI: 10.1093/jac/dkz368] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 07/05/2019] [Accepted: 07/25/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Diabetes mellitus (DM) is associated with poor TB treatment outcome. Previous studies examining the effect of DM on TB drug concentrations yielded conflicting results. No studies have been conducted to date in an African population. OBJECTIVES To compare exposure to TB drugs in Tanzanian TB patients with and without DM. PATIENTS AND METHODS A prospective pharmacokinetic study was performed among 20 diabetic and 20 non-diabetic Tanzanian TB patients during the intensive phase of TB treatment. Plasma pharmacokinetic parameters of isoniazid, rifampicin, pyrazinamide and ethambutol were compared using an independent-sample t-test on log-transformed data. Multiple linear regression analysis was performed to assess the effects of DM, gender, age, weight, HIV status and acetylator status on exposure to TB drugs. RESULTS A trend was shown for 25% lower total exposure (AUC0-24) to rifampicin among diabetics versus non-diabetics (29.9 versus 39.9 mg·h/L, P=0.052). The AUC0-24 and peak concentration (Cmax) of isoniazid were also lower in diabetic TB patients (5.4 versus 10.6 mg·h/L, P=0.015 and 1.6 versus 2.8 mg/L, P=0.013). Pyrazinamide AUC0-24 and Cmax values were non-significantly lower among diabetics (P=0.08 and 0.09). In multivariate analyses, DM remained an independent predictor of exposure to isoniazid and rifampicin, next to acetylator status for isoniazid. CONCLUSIONS There is a need for individualized dosing of isoniazid and rifampicin based on plasma concentration measurements (therapeutic drug monitoring) and for clinical trials on higher doses of these TB drugs in patients with TB and DM.
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Affiliation(s)
- Charles M Mtabho
- Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
| | - Hadija H Semvua
- Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
| | - Jossy van den Boogaard
- Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.,Radboud university medical center, Department of Lung Diseases & Radboud Institute for Health Sciences, Nijmegen, The Netherlands
| | - Constantine F Irongo
- Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.,National Tuberculosis and Leprosy Programme, Kilimanjaro Region, Tanzania
| | - Martin J Boeree
- Radboud university medical center, Department of Lung Diseases & Radboud Institute for Health Sciences, Nijmegen, The Netherlands
| | - Angela Colbers
- Radboud university medical center, Department of Pharmacy & Radboud Institute for Health Sciences, Nijmegen, The Netherlands
| | - David M Burger
- Radboud university medical center, Department of Pharmacy & Radboud Institute for Health Sciences, Nijmegen, The Netherlands
| | - Reinout van Crevel
- Radboud university medical center, Department of Internal Medicine & Radboud Institute for Health Sciences, Nijmegen, The Netherlands
| | - Andre J A M van der Ven
- Radboud university medical center, Department of Internal Medicine & Radboud Institute for Health Sciences, Nijmegen, The Netherlands
| | - Gibson S Kibiki
- Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
| | - Alma Tostmann
- Radboud university medical center, Department of Lung Diseases & Radboud Institute for Health Sciences, Nijmegen, The Netherlands
| | - Rob E Aarnoutse
- Radboud university medical center, Department of Pharmacy & Radboud Institute for Health Sciences, Nijmegen, The Netherlands
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17
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Oglesby W, Kara AM, Granados H, Cervantes JL. Metformin in tuberculosis: beyond control of hyperglycemia. Infection 2019; 47:697-702. [PMID: 31119504 DOI: 10.1007/s15010-019-01322-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 05/14/2019] [Indexed: 10/26/2022]
Abstract
Two global epidemics, diabetes mellitus (DM) and tuberculosis (TB), have converged making their control even more challenging. We herein have reviewed metformin's (MTF) effect on patients with active and latent TB, as well as discussed its newly discovered biological mechanisms in mycobacteria. Mounting evidence suggests that MTF provides better outcomes in TB patients, especially those with DM. The mechanisms by which MTF produces its benefits are multiple. Though metformin's potential has been proven in patients with DM, larger and more thorough clinical trials, in DM and non-DM-TB patients, need to be conducted. MTF could be added to the arsenal of anti-TB drugs, aiding in the goal of TB eradication worldwide.
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Affiliation(s)
- William Oglesby
- Department of Medical Education, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, 5001 El Paso Dr., El Paso, TX, 79905, USA
| | - Ali M Kara
- Department of Medical Education, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, 5001 El Paso Dr., El Paso, TX, 79905, USA
| | - Hector Granados
- Department of Pediatrics, Texas Tech University Health Sciences Center, El Paso, El Paso, TX, 79905, USA
| | - Jorge L Cervantes
- Department of Medical Education, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, 5001 El Paso Dr., El Paso, TX, 79905, USA.
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18
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Schalliol LA, Pittman JM, Ray SD. Insulin and other hypoglycemic drugs. SIDE EFFECTS OF DRUGS ANNUAL 2019:493-504. [DOI: 10.1016/bs.seda.2019.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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