ArticleClinical pharmacology and therapeutics2025
New Biomarkers for Renal Transporter-Mediated Drug-Drug Interactions: Metabolomic Effects of Cimetidine, Probenecid, Verapamil, and Rifampin in Humans.
Article in Clinical pharmacology and therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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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
6 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pyridoxic Acid as Endogenous Biomarker of Renal Organic Anion Transporter Activity: Population Variability and Mechanistic Modeling to Predict Drug-Drug Interactions.CPT: pharmacometrics & systems pharmacology · 2025Pooled it
- Effect of Late Second to Early Third Trimester of Pregnancy on the Activity of Renal Organic Anion Transporters (OAT1 and OAT3): A Biomarker Study.Clinical pharmacology and therapeutics · 2026Article
- Effects of Trimethoprim on Three Previously Proposed Putative Biomarkers for OCT2/MATE-Mediated Renal Drug-Drug Interactions in Healthy Volunteers.Clinical pharmacology and therapeutics · 2026Article
- Metabolomic and immunophenotypic signatures in cerebral amyloid angiopathy: a pilot study.Scientific reports · 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
- Putative new biomarkers for renal transporter-mediated drug-drug interactions: Characterization as substrates of organic cation transporter 2, multidrug and toxin extrusion protein 1, and other important drug transporters.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inhibition of renal transport proteins organic cation transporter 2 (OCT2), multidrug and toxin extrusion proteins (MATE1, MATE2-K), and organic anion transporters (OAT1, OAT3) causes clinically relevant drug-drug interactions (DDI). Endogenous biomarkers could be used to improve risk prediction of such renal DDIs. While a number of biomarkers for renal DDIs have been described so far, multiple criteria for valid biomarkers have frequently not been investigated, for example, specificity, metabolism, or food effects. Therefore, there is a need for novel biomarkers of renal DDIs. Here, we investigated the global metabolomic effects following the administration of two classical inhibitors of renal transport proteins [cimetidine (OCT2/MATEs), probenecid (OATs)] in human plasma and urine of healthy volunteers. Additionally, we investigated metabolomic effects of two inhibitors of other transporters [verapamil (P-glycoprotein), rifampin (organic anion transporting polypeptides)] as controls. This analysis shows that both cimetidine and probenecid affect compounds involved in caffeine metabolism, carnitines, and sulfates. Hierarchical cluster analysis of the effects of all four inhibitors on endogenous compounds identified multiple promising new sensitive and specific biomarker candidates for OCT2/MATE- or OAT-mediated DDIs. For OCT2/MATEs, 5-amino valeric acid betaine (median log
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