期刊
JOURNAL OF DAIRY SCIENCE
卷 99, 期 7, 页码 5731-5738出版社
ELSEVIER SCIENCE INC
DOI: 10.3168/jds.2015-10593
关键词
bovine ABCG2; polymorphism; enrofloxacin; ciprofloxacin
资金
- Spanish Ministry of Economy and Competitiveness (Madrid, Spain)
- European Regional Development Fund [AGL2012-31116, AGL2015-65626-R]
- Basque Government in Vitoria, Spain
- Garfi SAT farm (Santa Maria del Monte del Condado, Province of Leon, Spain)
The ATP-binding c.cssette transporter G2 (ABCG2) is involved in the secretion of several drugs into milk. The bovine Y581S ABCG2 polymorphism increases the secretion into milk of the fluoroquinolone danofloxacin in Holstein cows. Danofloxacin and enrofloxacin are the fluoroquinolones most widely used in veterinary medicine. Both enrofloxacin (ENRO) and its active metabolite ciprofloxacin (CIPRO) reach milk at relatively high concentrations. The aim of this work was to study the effect of the bovine Y581S ABCG2 polymorphism on in vitro transport as well as on concentrations in plasma and in milk of ENRO and CIPRO. Experiments using cells overexpressing bovine ABCG2 showed the effects of ABCG2 on the transport of CIPRO, demonstrating more efficient in vitro transport of this antimicrobial by the S581 variant as compared with the Y581 variant. Animal studies administering 2,5 mg/kg of ENRO subcutaneously to Y/Y 581 and Y/S 581 cows revealed that concentrations in plasma of FARO and CIPRO were significantly lower in YES animals. Regardless of the genotype, the antimicrobial profile in milk after the administration of ENRO was predominantly of CIPRO. With respect to the genotype effects on the amounts of drugs present in milk, AUC(0-24) values were more than 1,2 times higher in YES cows for ENRO and 2,2 times for CIPRO, indicating a greater capacity of Y581S to transfer these drugs into milk. These results emphasize the clinical relevance of this polymorphism as a factor affecting the concentrations in plasma and in milk of drugs of importance in veterinary medicine.
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