ABCG2 modulates chlorothiazide permeability--in vitro-characterization of its interactions.
Drug Metab Pharmacokinet
; 27(3): 349-53, 2012.
Article
en En
| MEDLINE
| ID: mdl-22790065
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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Permeabilidad de la Membrana Celular
/
Clorotiazida
/
Transportadoras de Casetes de Unión a ATP
/
Enterocitos
/
Diuréticos
/
Inhibidores de los Simportadores del Cloruro de Sodio
/
Proteínas de Neoplasias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Drug Metab Pharmacokinet
Asunto de la revista:
FARMACOLOGIA
/
METABOLISMO
Año:
2012
Tipo del documento:
Article
País de afiliación:
Hungria