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Interaction of enrofloxacin with breast cancer resistance protein (BCRP/ABCG2): influence of flavonoids and role in milk secretion in sheep
Author(s) -
PULIDO MIVIS M.,
MOLINA ANTONIO J.,
MERINO GRACIA,
MENDOZA GRACIA,
PRIETO JULIO G.,
ALVAREZ ANA I.
Publication year - 2006
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2006.00744.x
Subject(s) - abcg2 , efflux , pharmacology , chemistry , atp binding cassette transporter , enrofloxacin , multidrug resistance associated protein 2 , rhodamine 123 , pharmacokinetics , secretion , transporter , genistein , mastitis , multiple drug resistance , endocrinology , biology , biochemistry , ciprofloxacin , microbiology and biotechnology , gene , antibiotics
The ATP‐binding cassette (ABC) transporter breast cancer resistance protein (BCRP)/ABCG2 is a high‐capacity efflux transporter with wide substrate specificity located in apical membranes of epithelia, which is involved in drug availability. BCRP is responsible for the active secretion of clinically and toxicologically important substrates to milk. The present study shows BCRP expression in sheep and cow by immunoblotting with MAb (BXP‐53). Vanadate‐sensitive ATPase activity with specific BCRP substrates and inhibitors was measured in bovine mammary gland homogenates. To assess the role of BCRP in ruminant mammary gland we tested the fluoroquinolone enrofloxacin (ENRO). In polarized cell lines, ENRO was transported by Bcrp1/BCRP with secretory/absorptive ratios of 6.5 and 2 respectively. The efflux was blocked by the BCRP inhibitor Ko143. ENRO pharmacokinetics in plasma and milk was studied in sheep after co‐administration of drug (2.5 mg/kg, i.v.) and genistein (0.8 mg/kg, i.m.) or albendazole sulfoxide (2 mg/kg, i.v) as BCRP inhibitors. Concomitant administration of BCRP inhibitors with ENRO had no significant effect on the plasma disposition kinetics of ENRO but decreased ENRO concentrations in milk.