Trial reportPharmaceutical research2014
Investigation of endogenous compounds for assessing the drug interactions in the urinary excretion involving multidrug and toxin extrusion proteins.
Trial report in Pharmaceutical research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 60 citations in OpenAlex.
- Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.Clinical pharmacology and therapeutics · 2016Trial
- Recent advances in mass spectrometry-based bioanalytical methods for endogenous biomarkers analysis in transporter-mediated drug-drug interactions.Journal of pharmaceutical analysis · 2025Review
- Beyond ADME: The Endogenous Functions of Drug Transporters and Its Impact on Human Disease.Pharmaceutics · 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
- New Biomarkers for Renal Transporter-Mediated Drug-Drug Interactions: Metabolomic Effects of Cimetidine, Probenecid, Verapamil, and Rifampin in Humans.Clinical pharmacology and therapeutics · 2025Article
- Thiamine, gastrointestinal beriberi and acetylcholine signaling.Frontiers in nutrition · 2025Review
- Challenges of Serum Creatinine Level in GFR Assessment and Drug Dosing Decisions in Kidney Injury.Advanced pharmaceutical bulletin · 2024Review
- The Impacts of Slc19a3 Deletion and Intestinal SLC19A3 Insertion on Thiamine Distribution and Brain Metabolism in the Mouse.Metabolites · 2023Article
- Research Methods and New Advances in Drug-Drug Interactions Mediated by Renal Transporters.Molecules (Basel, Switzerland) · 2023Review
- Bile duct ligation differently regulates protein expressions of organic cation transporters in intestine, liver and kidney of rats through activation of farnesoid X receptor by cholate and bilirubin.Acta pharmaceutica Sinica. B · 2023Article
- Endogenous Biomarkers for SLC Transporter-Mediated Drug-Drug Interaction Evaluation.Molecules (Basel, Switzerland) · 2021Review
- Wernicke's encephalopathy - from basic science to clinical practice. Part 1: Understanding the role of thiamine.Therapeutic advances in psychopharmacology · 2020Review
- Influence of Transporter Polymorphisms on Drug Disposition and Response: A Perspective From the International Transporter Consortium.Clinical pharmacology and therapeutics · 2018Review
- Investigation of Glycochenodeoxycholate Sulfate and Chenodeoxycholate Glucuronide as Surrogate Endogenous Probes for Drug Interaction Studies of OATP1B1 and OATP1B3 in Healthy Japanese Volunteers.Pharmaceutical research · 2017Article
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- High-dose thiamine prevents brain lesions and prolongs survival of Slc19a3-deficient mice.PloS one · 2017Article
- Urinary Dopamine as a Potential Index of the Transport Activity of Multidrug and Toxin Extrusion in the Kidney.International journal of molecular sciences · 2016Article
- The first characterization of multidrug and toxin extrusion (MATE/SLC47) proteins in zebrafish (Danio rerio).Scientific reports · 2016Article
- Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3).Molecular pharmaceutics · 2015Article
- Involvement of organic cation transporters in the clearance and milk secretion of thiamine in mice.Pharmaceutical research · 2015Article
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMultidrug and toxin extrusion proteins (MATEs) are multispecific organic cation transporters mediating the efflux of various cationic drugs into the urine. The present study aimed at identifying endogenous compounds in human plasma and urine specimens as biomarkers to evaluate drug interactions involving MATEs in the kidney without administration of their exogenous probe drugs.
methodsAn untargeted metabolomic analysis was performed using urine and plasma samples from healthy volunteers and mice treated with or without the potent MATE inhibitor, pyrimethamine. Plasma and urinary concentrations of candidate markers were measured using liquid chromatography-mass spectrometry. Transport activities were determined in MATE- or OCT2-expressing HEK293 cells. The deuterium-labeled compounds of candidates were administered to mice for pharmacokinetics study.
resultsUrinary excretion of eleven compounds including thiamine and carnitine was significantly lower in the pyrimethamine-treatment group in humans and mice, whereas no endogenous compound was noticeably accumulated in the plasma. The renal clearance of thiamine and carnitine was decreased by 70%-84% and 90%-94% (p < 0.05), respectively, in human. The specific uptake of thiamine was observed in MATE1-, MATE2-K- or OCT2-expressing HEK293 cells with Km of 3.5 ± 1.0, 3.9 ± 0.8 and 59.9 ± 6.7 μM, respectively. The renal clearance of carnitine-d 3 was decreased by 62% in mice treated with pyrimethamine.
conclusionsOur findings indicate that MATEs account for the efflux of thiamine and perhaps carnitine as well as drugs into the urine. The urinary excretion of thiamine is useful to detect drug interaction involving MATEs in the kidney.
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Registered trials
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 OpenQuestion graph.