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)

[thumbnail of drug_metabolism2012.pdf] Text
drug_metabolism2012.pdf - Published Version

Download (761kB)
Item Type: Article
Creators:
CreatorsORCIDMTMT szerző azonosító
Beéry Erzsébet
Narozsnikné Rajnai Zsuzsanna10044158
Abonyi Tibor
Makai Ildikó
Bánsághi Száva0000-0002-0742-398410061310
Erdő Franciska10044620
Sziráki István
Herédi-Szabó Krisztina
Kis Emese10089178
Jani Márton10054067
Márki-Zay János10026015
Tóth Gábor0000-0002-3604-438510000556
Krajcsi Péter0000-0002-4450-595410009464
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: 27
Number: 3
Page Range: pp. 349-353
ISSN: 1347-4367
Institution: Pázmány Péter Katolikus Egyetem
Kar: Információs Technológiai Kar (1998-2013.06.)
Nyelv: angol
MTMT rekordazonosító: 1765884
DOI azonosító: 10.2133/dmpk.DMPK-11-NT-068
Scopus azonosító: 84863191353
WoS azonosító: 000305597900011
Date Deposited: 2025. Mar. 07. 13:24
Last Modified: 2025. Mar. 07. 13:24
URI: https://publikacio.ppke.hu/id/eprint/2382

Actions (login required)

View Item View Item