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The Bovine ATP-binding Cassette Transporter ABCG2 Y581S Single Nucleotide Polymorphism Increases Milk Secretion of the Fluoroquinolone Danofloxacin.


Drug Metab Dispos. 2012 Dec 10;


Authors: Otero JA, Real R, de la Fuente A, Prieto JG, Marques M, Alvarez AI, Merino G


Abstract

The bovine ATP-binding cassette transporter ABCG2 [Breast Cancer Resistant Protein (BCRP)] polymorphism Y581S has recently been shown to increase in vitro transepithelial transport of antibiotics. Since this transporter has been extensively related to the active secretion of drugs into milk, the potential in vivo effect of this polymorphism on secretion of xenobiotics in livestock could have striking consequences for milk production, the dairy industry and Public Health. Our purpose was to study the in vivo effect of this polymorphism on the secretion into milk of danofloxacin, a widely used veterinary antibiotic. Danofloxacin (1.25 mg/kg) was administered to six Y/Y 581 homozygous and six Y/S 581 heterozygous lactating cows, and plasma and milk samples were collected and analysed by HPLC. No differences were found in the pharmacokinetic parameters of danofloxacin in plasma between the two groups of animals. In contrast, Y/S heterozygous cows showed a two-fold increase in danofloxacin levels in milk. In addition, the pharmacokinetic elimination parameters MRT and T(1/2el) were significantly lower in the milk of the animals carrying the Y/S polymorphism. These in vivo results are in agreement with our previously published in vitro data, which showed a greater capacity of the S581 variant in accumulation assays, and demonstrate for the first time an important effect of the Y581S SNP on antibiotic secretion into cow milk. These findings could be extended to other ABCG2 substrates and may be relevant for the treatment of mastitis and for the design of accurate and novel strategies to handle milk residues.

PMID: 23230133 [PubMed - as supplied by publisher]