ABCG2 modulates chlorothiazide permeability in vitro – characterization of the interaction

Beéry Erzsébet and Narozsnikné Rajnai Zsuzsanna and Abonyi Tibor and Makai Ildikó and Bánsághi Száva and Erdő Franciska and Sziráki István and Herédi-Szabó Krisztina and Kis Emese and Jani Márton and Márki-Zay János and Tóth Gábor and Krajcsi Péter: ABCG2 modulates chlorothiazide permeability in vitro – characterization of the interaction.
DRUG METABOLISM AND PHARMACOKINETICS, 27 (3). pp. 349-353. ISSN 1347-4367 (2012)

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Item Type:

Article

Creators:

Creators	ORCID	MTMT szerző azonosító
Beéry Erzsébet
Narozsnikné Rajnai Zsuzsanna		10044158
Abonyi Tibor
Makai Ildikó
Bánsághi Száva	0000-0002-0742-3984	10061310
Erdő Franciska		10044620
Sziráki István
Herédi-Szabó Krisztina
Kis Emese		10089178
Jani Márton		10054067
Márki-Zay János		10026015
Tóth Gábor	0000-0002-3604-4385	10000556
Krajcsi Péter	0000-0002-4450-5954	10009464

Abstract:

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.

Journal or Publication Title:

DRUG METABOLISM AND PHARMACOKINETICS

Date:

2012

Volume:

Number:

Page Range:

pp. 349-353

ISSN:

1347-4367

Institution:

Pázmány Péter Katolikus Egyetem