The inhibitory effects of eighteen front-line antibiotics on the substrate uptake mediated by human Organic anion/cation transporters, Organic anion transporting polypeptides and Oligopeptide transporters in in vitro models

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Xiaoxi LuFanfan Zhou

Abstract

Human Organic anion/cation transporters (OATs/OCTs), Organic anion transporting polypeptides (OATPs) and proton-coupled Oligopeptide transporters (PepTs) are important membrane transporters responsible of the cellular influx of drugs in many human key tissues. Inhibitor(s) impacting on the cellular uptake of transporter drug substrates is one of the primary causes of drug-drug interactions that lead to unsatisfied therapeutic outcomes and/or unwanted side effects. In the current study, we selected eighteen antibiotic agents used in infectious disease treatment and comprehensively evaluated their inhibitory effects on the substrate uptake mediated through the essential OATs/OCTs, OATPs and PepTs isoforms. Transport functional assay, dose-response curve and kinetic analysis were performed on the HEK293 cells over-expressing each of these transporter genes. Our data revealed that nitrofurantoin, sulfadiazine and metronidazole significantly inhibited the transport activity of OAT3 (IC50 values of 6.23±1.33μM, 6.65±1.30μM and 6.51±0.99μM; Ki values of 5.86μM, 3.98μM and 6.48μM, respectively). Trimethoprim and ciprofloxacin potently decreased the substrate uptake mediated via OATP1A2 (IC50 values of 9.35±1.10μM and 9.25±1.18μM; Ki va...Continue Reading

Citations

Mar 21, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Iichiro KawaharaTakuya Fujita
Sep 1, 2018·European Journal of Clinical Pharmacology·Hannah Yejin KimAlan V Boddy
Nov 30, 2018·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Jasmine L GowartyJon D Herrington
Sep 30, 2020·Current Drug Metabolism·Xuan YuChen Cheng

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