title: Interaction of enrofloxacin with breast cancer resistance protein (BCRP/ABCG2): influence of flavonoids and role in milk secretion in sheep.
abstract: 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.
authors.affiliation: Department of Physiology, Faculty of Veterinary Medicine, University of Leon, Leon, Spain.
authors.forename: Mivis M
authors.initials: MM
authors.lastname: Pulido
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Molina
authors.forename: Gracia
authors.initials: G
authors.lastname: Merino
authors.forename: Gracia
authors.initials: G
authors.lastname: Mendoza
authors.forename: Julio G
authors.initials: JG
authors.lastname: Prieto
authors.forename: Ana I
authors.initials: AI
authors.lastname: Alvarez
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D015766:Albendazole / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001693:Biological Transport, Active; D002417:Cattle / Q000378:metabolism*; D004285:Dogs; D018432:Drug Resistance, Multiple; D000077422:Enrofloxacin; D005260:Female; D044950:Flavanones / Q000008:administration & dosage / Q000494:pharmacology; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D007774:Lactation; D008321:Mammary Glands, Animal / Q000187:drug effects*; D051379:Mice; D008892:Milk / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D012756:Sheep / Q000378:metabolism*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D000970:Antineoplastic Agents; D044950:Flavanones; D024841:Fluoroquinolones; D009363:Neoplasm Proteins; D000077422:Enrofloxacin; D019833:Genistein; D015766:Albendazole; C027186:albendazole sulfoxide