ArticleClinical pharmacology and therapeutics2022
Blockade of Organic Anion Transport in Humans After Treatment With the Drug Probenecid Leads to Major Metabolic Alterations in Plasma and Urine.
Article in Clinical pharmacology and therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses 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.
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
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 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
- Hyperuricemia and the gut microbiota: current research hotspots and future trends.Frontiers in microbiology · 2025Pooled it
- Untargeted Metabolomics Reveal New Endogenous Plasma Biomarkers Associated with CYP3A Inhibition in Humans.Clinical pharmacology and therapeutics · 2026Article
- 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
- A Kidney-Microbiome Short- and Medium-Chain Fatty Acid Loop Mediated by OAT1: Implications for the Remote Sensing and Signaling Theory.International journal of molecular sciences · 2026Article
- Enteronephrohepatic circulation of bile acids and therapeutic potential of systemic bile acid transporter inhibitors.Journal of hepatology · 2025Review
- From Discovery to Translation: Endogenous Substrates of OAT1 and OAT3 as Clinical Biomarkers for Renal Secretory Function.Clinical pharmacology and therapeutics · 2025Article
- Drug Exposure in Chronic Kidney Disease: It Is Not Just About the Glomerular Filtration Rate.Fundamental & clinical pharmacology · 2025Review
- Furosemide and Serum Protein-Bound Uremic Toxin Concentrations in Patients With CKD.Kidney international reports · 2025Article
- Hyperuricemia-induced complications: dysfunctional macrophages serve as a potential bridge.Frontiers in immunology · 2025Review
- New Biomarkers for Renal Transporter-Mediated Drug-Drug Interactions: Metabolomic Effects of Cimetidine, Probenecid, Verapamil, and Rifampin in Humans.Clinical pharmacology and therapeutics · 2025Article
- Pannexin channels in inflammation and tumorigenesis.Frontiers in cell and developmental biology · 2025Review
- Drug-Drug Interactions in Nosocomial Infections: An Updated Review for Clinicians.Pharmaceutics · 2024Review
- In Vivo Regulation of Small Molecule Natural Products, Antioxidants, and Nutrients by OAT1 and OAT3.Nutrients · 2024Article
- Article
- 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
- Emerging Urate-Lowering Drugs and Pharmacologic Treatment Strategies for Gout: A Narrative Review.Drugs · 2023Review
- The substrate and inhibitor binding mechanism of polyspecific transporter OAT1 revealed by high-resolution cryo-EM.Nature structural & molecular biology · 2023Article
- Suppression of Indoxyl Sulfate Accumulation Reduces Renal Fibrosis in Sulfotransferase 1a1-Deficient Mice.International journal of molecular sciences · 2023Article
- Loss of the Kidney Urate Transporter, Urat1, Leads to Disrupted Redox Homeostasis in Mice.Antioxidants (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Probenecid is used to treat gout and hyperuricemia as well as increase plasma levels of antiviral drugs and antibiotics. In vivo, probenecid mainly inhibits the renal SLC22 organic anion transporters OAT1 (SLC22A6), OAT3 (SLC22A8), and URAT1 (SLC22A12). To understand the endogenous role of these transporters in humans, we administered probenecid to 20 healthy participants and metabolically profiled the plasma and urine before and after dosage. Hundreds of metabolites were significantly altered, indicating numerous drug-metabolite interactions. We focused on potential OAT1 substrates by identifying 97 metabolites that were significantly elevated in the plasma and decreased in the urine, indicating OAT-mediated clearance. These included signaling molecules, antioxidants, and gut microbiome products. In contrast, urate was the only metabolite significantly decreased in the plasma and elevated in the urine, consistent with an effect on renal reuptake by URAT1. Additional support comes from metabolomics analyses of our Oat1 and Oat3 knockout mice, where over 50% of the metabolites that were likely OAT substrates in humans were elevated in the serum of the mice. Fifteen of these compounds were elevated in both knockout mice, whereas six were exclusive to the Oat1 knockout and 4 to the Oat3 knockout. These may be endogenous biomarkers of OAT function. We also propose a probenecid stress test to evaluate kidney proximal tubule organic anion transport function in kidney disease. Consistent with the Remote Sensing and Signaling Theory, the profound changes in metabolite levels following probenecid treatment support the view that SLC22 transporters are hubs in the regulation of systemic human metabolism.
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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.