Evidence for the Validity of Pyridoxic Acid (PDA) as a Plasma-Based Endogenous Probe for OAT1 and OAT3 Function in Healthy Subjects
| Autor: | T. Thanga Mariappan, Petia Shipkova, Joseph L. Cantone, Prabhakar Rajanna, Hong Shen, Jinping Gan, W. Griffith Humphreys, Shashyendra Singh Gautam, Dieter M. Drexler, Yueping Zhang, Vinay K. Holenarsipur, Punit Marathe |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Pyridoxic Acid Adolescent Organic anion transporter 1 Endogeny Organic Anion Transporters Sodium-Independent Pharmacology Young Adult 03 medical and health sciences chemistry.chemical_compound Organic Anion Transport Protein 1 0302 clinical medicine Healthy volunteers Humans Medicine Cross-Over Studies biology business.industry Homovanillic acid Reproducibility of Results Furosemide Middle Aged Crossover study Healthy Volunteers Probenecid 030104 developmental biology chemistry biology.protein Molecular Medicine business Biomarkers 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 368:136-145 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.118.252643 |
| Popis: | Plasma pyridoxic acid (PDA) and homovanillic acid (HVA) were recently identified as novel endogenous biomarkers of organic anion transporter (OAT) 1/3 function in monkeys. Consequently, this clinical study assessed the dynamic changes and utility of plasma PDA and HVA as an initial evaluation of OAT1/3 inhibition in early-phase drug development. The study was designed as a single-dose randomized, three-phase, crossover study; 14 Indian healthy volunteers received probenecid (PROB) (1000 mg orally) alone, furosemide (FSM) (40 mg orally) alone, or FSM 1 hour after receiving PROB (40 and 1000 mg orally) on days 1, 8, and 15, respectively. PDA and HVA plasma concentrations remained stable over time in the prestudy and FSM groups. Administration of PROB significantly increased the area under the plasma concentration-time curve (AUC) of PDA by 3.1-fold (dosed alone; P 0.05) and 2.1-fold (P |
| Databáze: | OpenAIRE |
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