05/11/2013 - Role of transporters in drug ADME
Erzsébet Beéry, Zsuzsanna Rajnai, Tibor Abonyi, Ildikó Makai, Száva Bánsághy, Franciska Erdő, István Sziráki, Emese Kis, Márton Jani, Gábor K Tóth, Peter Krajcsi Drug Metab Pharmacokinet. 2011 Nov 29.
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 Km 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.open_in_new Read the Source