ArticleBritish journal of clinical pharmacology2013
Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 transporters.
Article in British journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04930744 (A Prospective, Randomized Open-Label Phase II Study of the Safety and Tolerability of Metformin in Combination With Standard Antimicrobial Treatment of Pulmonary Tuberculosis in People Co-infected With HIV), which is not on this map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Prospective, Randomized Open-Label Phase II Study of the Safety and Tolerability of Metformin in Combination With Standard Antimicrobial Treatment of Pulmonary Tuberculosis in People Co-infected With HIV
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Improving antibacterial prescribing safety in the management of COPD exacerbations: systematic review of observational and clinical studies on potential drug interactions associated with frequently prescribed antibacterials among COPD patients.The Journal of antimicrobial chemotherapy · 2019Pooled it
- Evaluation of OCT2-mediated drug-drug interactions between ulotaront and metformin in subjects with schizophrenia.Pharmacology research & perspectives · 2024Trial
- Identification of Appropriate Endogenous Biomarker for Risk Assessment of Multidrug and Toxin Extrusion Protein-Mediated Drug-Drug Interactions in Healthy Volunteers.Clinical pharmacology and therapeutics · 2021Trial
- N(1)-methylnicotinamide as an endogenous probe for drug interactions by renal cation transporters: studies on the metformin-trimethoprim interaction.European journal of clinical pharmacology · 2015Trial
- Near-fatal reaction associated with cotrimoxazole, metformin and kidney impairment.Australian prescriber · 2025Article
- Predicting OCT2/MATEs-Mediated Drug Interactions in Healthy Volunteers and Patients with Chronic Kidney Disease: Insights from Extended Clearance Concept, Endogenous Biomarkers, and In Vitro Inhibition Studies (Perspectives from the International Transporter Consortium).Clinical pharmacology and therapeutics · 2025Review
- Silent Dangers in Elderly Pharmacotherapy: The Interplay of Polypharmacy, Multimorbidity, and Drug Interactions.Journal of evaluation in clinical practice · 2025Review
- Substrate-specific inhibition of organic cation transporter 1 revealed using a multisubstrate drug cocktail.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Effects of Cimetidine and Dolutegravir on the Endogenous Drug-Drug Interaction Biomarkers for Organic Cation Transporter 2 and Multidrug and Toxin Extrusion Protein 1 in Healthy Volunteers.Clinical pharmacology and therapeutics · 2025Article
- No dose adjustment of metformin or substrates of organic cation transporters (OCT)1 and OCT2 and multidrug and toxin extrusion protein (MATE)1/2K with fostemsavir coadministration based on modeling approaches.Pharmacology research & perspectives · 2024Article
- Insight into Risk Factors, Pharmacogenetics/Genomics, and Management of Adverse Drug Reactions in Elderly: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The Issue of Pharmacokinetic-Driven Drug-Drug Interactions of Antibiotics: A Narrative Review.Antibiotics (Basel, Switzerland) · 2022Review
- The determination of the effect(s) of solute carrier family 22-member 2 (SLC22A2) haplotype variants on drug binding via molecular dynamic simulation systems.Scientific reports · 2022Article
- Metformin serum concentrations during pregnancy and post partum - A clinical study in patients with polycystic ovary syndrome.Basic & clinical pharmacology & toxicology · 2022Article
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- Membrane Carriers and Transporters in Kidney Physiology and Disease.Biomedicines · 2021Review
- Article
- Clinically Relevant Interactions between Atypical Antipsychotics and Anti-Infective Agents.Pharmaceuticals (Basel, Switzerland) · 2020Review
- A Physiologically-Based Pharmacokinetic Model of Trimethoprim for MATE1, OCT1, OCT2, and CYP2C8 Drug-Drug-Gene Interaction Predictions.Pharmaceutics · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsMetformin pharmacokinetics depends on the presence and activity of membrane-bound drug transporters and may be affected by transport inhibitors. The aim of this study was to investigate the effects of trimethoprim on metformin pharmacokinetics and genetic modulation by organic cation transporter 2 (OCT2) and multidrug and toxin extrusion 1 (MATE1) polymorphisms.
methodsTwenty-four healthy volunteers received metformin 500 mg three times daily for 10 days and trimethoprim 200 mg twice daily from day 5 to 10. Effects of trimethoprim on steady-state metformin pharmacokinetics were analysed.
resultsIn the population as a whole, trimethoprim significantly reduced the apparent systemic metformin clearance (CL/F) from 74 to 54 l h(-1) and renal metformin clearance from 31 to 21 l h(-1) , and prolonged half-life from 2.7 to 3.6 h (all P < 0.01). This resulted in an increase in the maximal plasma concentration by 38% and in the area under the plasma concentration-time curve by 37%. In volunteers polymorphic for both OCT2 and MATE1, trimethoprim had no relevant inhibitory effects on metformin kinetics. Trimethoprim was associated with a decrease in creatinine clearance from 133 to 106 ml min(-1) (P < 0.01) and an increase in plasma lactate from 0.94 to 1.2 mmol l(-1) (P = 0.016).
conclusionsThe extent of inhibition by trimethoprim was moderate, but might be clinically relevant in patients with borderline renal function or high-dose metformin.
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Registered trials
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