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ABCG2 Modulates Chlorothiazide Permeability <i>In Vitro</i>-characterization of Its Interactions.

Drug Metab Pharmacokinet. 2012 Jun 25;27(3):349-53

Authors: Beéry E, Rajnai Z, Abonyi T, Makai I, Bánsághi S, Erdő F, Sziráki I, Herédi-Szabó K, Kis E, Jani M, Márki-Zay J, Tóth K G, Krajcsi P


We are showing that chlorothiazide, a diuretic, is an ABCG2 substrate. It is a Biopharmaceutics Classification System/Biopharmaceutics Drug Distribution and Classification System (BCS/BDDCS) Class IV drug with low bioavailability. Therefore, we tested if chlorothiazide interacts with major apically located intestinal efflux transporters. Our data show that chlorothiazide is transported by ABCG2 with a K<inf>m</inf> value of 334.6 µM and does not interact with ABCB1 or ABCC2. The chlorothiazide-ABCG2 interaction results in a vectorial transport in MDCKII-BCRP and Caco-2 cells with efflux ratios of 36 and 8.1 respectively. Inhibition of ABCG2 in Caco-2 cells reduced the efflux ratio to 1.4, suggesting that ABCG2 plays a role in limiting chlorothiazide bioavailability in humans.

PMID: 22790065 [PubMed - in process]