ABCG2 modulates chlorothiazide permeability in vitro – characterization of the interaction

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 apic...

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Bibliographic Details
Main Authors: Beéry Erzsébet
Narozsnikné Rajnai Zsuzsanna
Abonyi Tibor
Makai Ildikó
Bánsághi Száva
Erdő Franciska
Sziráki István
Herédi-Szabó Krisztina
Kis Emese
Jani Márton
Márki-Zay János
Tóth Gábor
Krajcsi Péter
Format: Article
Published: 2012
Series:DRUG METABOLISM AND PHARMACOKINETICS 27 No. 3
Subjects:
Farmakológia és gyógyszerészet
doi:10.2133/dmpk.DMPK-11-NT-068

mtmt:1765884
Online Access:https://publikacio.ppke.hu/2382
Description
Summary: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.
Physical Description:349-353
ISSN:1347-4367

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