Evidence mapPaperPMID 39148267Full record

ArticleClinical pharmacology and therapeutics2025

New Biomarkers for Renal Transporter-Mediated Drug-Drug Interactions: Metabolomic Effects of Cimetidine, Probenecid, Verapamil, and Rifampin in Humans.

Arne Gessner, Jörg König, Pia Wenisch, Markus R Heinrich, Peter Stopfer, Martin F Fromm, Fabian Müller

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  3. Article
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  5. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Arne GessnerInstitute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.ORCID 0000-0002-1729-4231
Jörg KönigInstitute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.ORCID 0000-0001-7016-5482
Pia WenischDepartment of Chemistry and Pharmacy, Pharmaceutical Chemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.ORCID 0000-0001-6542-323X
Markus R HeinrichFAU NeW - Research Center New Bioactive Compounds, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.ORCID 0000-0001-7113-2025
Peter StopferBoehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.ORCID 0000-0003-0144-0895
Martin F FrommInstitute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.ORCID 0000-0002-0334-7478
Fabian MüllerInstitute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.ORCID 0000-0002-0483-0293

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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

Indexed as

BiomarkersCimetidineDrug InteractionsMetabolomicsOrganic Cation Transporter 2Organic Cation Transport ProteinsProbenecidRifampinVerapamilAdultFemaleHumansKidneyMaleOrganic Anion TransportersOrganic Anion Transporters, Sodium-IndependentBiomarkersCimetidineOrganic Anion TransportersOrganic Anion Transporters, Sodium-IndependentOrganic Anion Transport Protein 1organic anion transport protein 3Organic Cation Transporter 2Organic Cation Transport ProteinsProbenecidRifampinSLC22A2 protein, humanSLC47A1 protein, humanSLC47A2 protein, humanVerapamil

Identifiers

PMID39148267
PMCPMC11652812

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.