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1. Febuxostat and its major acyl glucuronide metabolite are potent inhibitors of organic anion transporter 3: Implications for drug-drug interactions with rivaroxaban

Author

Lloyd Wei Tat Tang, Tino Woon Huai Cheong, and Eric Chun Yong Chan

Subjects
Pharmacology, Febuxostat, Glucuronides, HEK293 Cells, Organic Anion Transport Protein 1, Rivaroxaban, Pharmaceutical Science, Humans, Pharmacology (medical), Drug Interactions, General Medicine, Organic Anion Transporters, Sodium-Independent
Abstract

Febuxostat is a second-line xanthine oxidase inhibitor that undergoes extensive hepatic metabolism to yield its major acyl-β-D-glucuronide metabolite (febuxostat AG). It was recently reported that febuxostat inhibited organic anion transporter 3 (OAT3)-mediated uptake of enalaprilat. Here, we investigated the inhibition of febuxostat and febuxostat AG on OAT3 in transfected human embryonic kidney 293 cells. Our transporter inhibition assays confirmed the potent noncompetitive and competitive inhibition of OAT3-mediated estrone-3-sulfate transport by febuxostat and febuxostat AG with corresponding apparent K

Published
2022

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