ABCG2 modulates chlorothiazide permeability--in vitro-characterization of its interactions.
Drug Metab Pharmacokinet
; 27(3): 349-53, 2012.
Article
in 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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Membrane Permeability
/
Chlorothiazide
/
ATP-Binding Cassette Transporters
/
Enterocytes
/
Diuretics
/
Sodium Chloride Symporter Inhibitors
/
Neoplasm Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
Drug Metab Pharmacokinet
Journal subject:
FARMACOLOGIA
/
METABOLISMO
Year:
2012
Document type:
Article
Affiliation country: