Trial reportEuropean journal of clinical pharmacology2015
N(1)-methylnicotinamide as an endogenous probe for drug interactions by renal cation transporters: studies on the metformin-trimethoprim interaction.
Trial report in European journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 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
- 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
- Limited sampling strategy for determining metformin area under the plasma concentration-time curve.British journal of clinical pharmacology · 2016Trial
- Endogenous Biomarkers to Evaluate Transporter-Mediated Drug-Drug Interactions: Current Evidence, Impact on Clinical Pharmacology Strategy, Remaining Gaps, and Future Directions.Journal of clinical pharmacology · 2026Review
- 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
- Recent advances in mass spectrometry-based bioanalytical methods for endogenous biomarkers analysis in transporter-mediated drug-drug interactions.Journal of pharmaceutical analysis · 2025Review
- Quantitative Contributions of Hepatic and Renal Organic Cation Transporters to the Clinical Pharmacokinetic Cimetidine-Metformin Interaction.Clinical pharmacology and therapeutics · 2025Article
- Precision medication based on the evaluation of drug metabolizing enzyme and transporter functions.Precision clinical medicine · 2025Review
- 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
- IsMetabolites · 2025Article
- New Biomarkers for Renal Transporter-Mediated Drug-Drug Interactions: Metabolomic Effects of Cimetidine, Probenecid, Verapamil, and Rifampin in Humans.Clinical pharmacology and therapeutics · 2025Article
- Challenges of Serum Creatinine Level in GFR Assessment and Drug Dosing Decisions in Kidney Injury.Advanced pharmaceutical bulletin · 2024Review
- 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
- Expanding Role of Endogenous Biomarkers for Assessment of Transporter Activity in Drug Development: Current Applications and Future Horizon.Pharmaceutics · 2024Article
- Utilising Endogenous Biomarkers in Drug Development to Streamline the Assessment of Drug-Drug Interactions Mediated by Renal Transporters: A Pharmaceutical Industry Perspective.Clinical pharmacokinetics · 2024Review
- Impact of Pregnancy on the Pharmacokinetics and Metabolism of Nicotinamide in Humans.Clinical pharmacology and therapeutics · 2024Article
- Effect of Cimetidine on Metformin Pharmacokinetics and Endogenous Metabolite Levels in Rats.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Albumin-bound kynurenic acid is an appropriate endogenous biomarker for assessment of the renal tubular OATs-MRP4 channel.Journal of pharmaceutical analysis · 2023Article
- Research Methods and New Advances in Drug-Drug Interactions Mediated by Renal Transporters.Molecules (Basel, Switzerland) · 2023Review
- Evaluation of the Effect of Abrocitinib on Drug Transporters by Integrated Use of Probe Drugs and Endogenous Biomarkers.Clinical pharmacology and therapeutics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeN(1)-methylnicotinamide (NMN) was proposed as an in vivo probe for drug interactions involving renal cation transporters, which, for example, transport the oral antidiabetic drug metformin, based on a study with the inhibitor pyrimethamine. The role of NMN for predicting other interactions with involvement of renal cation transporters (organic cation transporter 2, OCT2; multidrug and toxin extrusion proteins 1 and 2-K, MATE1 and MATE2-K) is unclear.
methodsWe determined inhibition of metformin or NMN transport by trimethoprim using cell lines expressing OCT2, MATE1, or MATE2-K. Moreover, a randomized, open-label, two-phase crossover study was performed in 12 healthy volunteers. In each phase, 850 mg metformin hydrochloride was administered p.o. in the evening of day 4 and in the morning of day 5. In phase B, 200 mg trimethoprim was administered additionally p.o. twice daily for 5 days. Metformin pharmacokinetics and effects (measured by OGTT) and NMN pharmacokinetics were determined.
resultsTrimethoprim inhibited metformin transport with K i values of 27.2, 6.3, and 28.9 μM and NMN transport with IC50 values of 133.9, 29.1, and 0.61 μM for OCT2, MATE1, and MATE2-K, respectively. In the clinical study, trimethoprim increased metformin area under the plasma concentration-time curve (AUC) by 29.5 % and decreased metformin and NMN renal clearances by 26.4 and 19.9 %, respectively (p ≤ 0.01). Moreover, decreases of NMN and metformin renal clearances due to trimethoprim correlated significantly (r S=0.727, p=0.010).
conclusionsThese data on the metformin-trimethoprim interaction support the potential utility of N(1)-methylnicotinamide as an endogenous probe for renal drug-drug interactions with involvement of renal cation transporters.
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