ArticleClinical pharmacokinetics2021
Clinical Investigation on Endogenous Biomarkers to Predict Strong OAT-Mediated Drug-Drug Interactions.
Article in Clinical pharmacokinetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers, 1 of them a synthesis that pooled it.
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.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- 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
- Dicloxacillin and Flucloxacillin Inhibit Hepatic Uptake Transporters-In Vitro Investigations and Physiologically Based Pharmacokinetic Modeling.Clinical and translational science · 2026Article
- Enhancing therapeutic strategies and drug development for patients with kidney disease.Expert opinion on drug safety · 2026Review
- Population Pharmacokinetic Modeling of Glycochenodeoxycholic Acid 3-O-Sulfate (GCDCA-S) as Endogenous Biomarker of OATP1B3 and OAT3 Transporters.Clinical pharmacology and therapeutics · 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
- Recent advances in mass spectrometry-based bioanalytical methods for endogenous biomarkers analysis in transporter-mediated drug-drug interactions.Journal of pharmaceutical analysis · 2025Review
- Dicloxacillin and flucloxacillin inhibit hepatic uptake transporters -in vitro investigations and physiologically based pharmacokinetic modelling.bioRxiv : the preprint server for biology · 2025Article
- From Discovery to Translation: Endogenous Substrates of OAT1 and OAT3 as Clinical Biomarkers for Renal Secretory Function.Clinical pharmacology and therapeutics · 2025Article
- Drug Interaction PBPK Modeling: Review of the Literature Exposes the Need for Increased Verification of Model Inputs and Outputs as Part of Credibility Assessment.Clinical and translational science · 2025Review
- Evaluation of Adefovir PBPK Model to Assess Biomarker-Informed OAT1 Drug-Drug Interaction and Effect of Chronic Kidney Disease.CPT: pharmacometrics & systems pharmacology · 2025Article
- Precision medication based on the evaluation of drug metabolizing enzyme and transporter functions.Precision clinical medicine · 2025Review
- 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
- Membrane transporters in drug development and as determinants of precision medicine.Nature reviews. Drug discovery · 2024Review
- Review
- Identification of three distinct cell populations for urate excretion in human kidneys.The journal of physiological sciences : JPS · 2024Article
- Effect of probenecid on blood levels and renal elimination of furosemide and endogenous compounds in rats: Discovery of putative organic anion transporter biomarkers.Biochemical pharmacology · 2023Article
- Blockade of Organic Anion Transport in Humans After Treatment With the Drug Probenecid Leads to Major Metabolic Alterations in Plasma and Urine.Clinical pharmacology and therapeutics · 2022Article
- Effect of Chronic Kidney Disease on the Renal Secretion via Organic Anion Transporters 1/3: Implications for Physiologically-Based Pharmacokinetic Modeling and Dose Adjustment.Clinical pharmacology and therapeutics · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEndogenous biomarkers are promising tools to assess transporter-mediated drug-drug interactions early in humans.
methodsWe evaluated on a common and validated in vitro system the selectivity of 4-pyridoxic acid (PDA), homovanillic acid (HVA), glycochenodeoxycholate-3-sulphate (GCDCA-S) and taurine towards different renal transporters, including multidrug resistance-associated protein, and assessed the in vivo biomarker sensitivity towards the strong organic anion transporter (OAT) inhibitor probenecid at 500 mg every 6 h to reach close to complete OAT inhibition.
resultsPDA and HVA were substrates of the OAT1/2/3, OAT4 (PDA only) and multidrug resistance-associated protein 4; GCDCA-S was more selective, having affinity only towards OAT3 and multidrug resistance-associated protein 2. Taurine was not a substrate of any of the investigated transporters under the in vitro conditions tested. Plasma exposure of PDA and HVA significantly increased and the renal clearance of GCDCA-S, PDA and HVA decreased; the magnitude of these changes was comparable to those of known clinical OAT probe substrates. PDA and GCDCA-S were the most promising endogenous biomarkers of the OAT pathway activity: PDA plasma exposure was the most sensitive to probenecid inhibition, and, in contrast, GCDCA-S was the most sensitive OAT biomarker based on renal clearance, with higher selectivity towards the OAT3 transporter.
conclusionsThe current findings illustrate a clear benefit of measuring PDA plasma exposure during phase I studies when a clinical drug candidate is suspected to be an OAT inhibitor based on in vitro data. Subsequently, combined monitoring of PDA and GCDCA-S in both urine and plasma is recommended to tease out the involvement of OAT1/3 in the inhibition interaction. CLINICAL
trial registrationEudraCT number: 2016-003923-49.
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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 OpenQuestion graph.