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    Título
    Role of ABCG2 in secretion into milk of the anti-inflammatory flunixin and its main metabolite: in vitro-in vivo correlation in mice and cows
    Autor
    García Mateos, Dafne
    Garcia-Lino, Alba Maria
    Alvarez-Fernandez, Indira
    Blanco-Paniagua, Esther
    Fuente, Álvaro de la
    Álvarez de Felipe, Ana IsabelAutoridad BuleriaORCID
    Merino Peláez, GraciaAutoridad BuleriaORCID
    Facultad/Centro
    Facultad de Veterinaria
    Área de conocimiento
    Fisiologia
    Datos de la obra
    Drug Metabolism and Disposition
    Editor
    ASPET
    Fecha
    2019-04-23
    Abstract
    Flunixin meglumine is a nonsteroidal anti-inflammatory drug (NSAID) widely used in veterinary medicine. It is indicated to treat inflammatory processes, pain and pyrexia in farm animals. In addition, it is one of the few NSAIDs approved for use in dairy cows, and consequently gives rise to concern regarding its milk residues. The ABCG2 efflux transporter is induced during lactation in the mammary gland and plays an important role in the secretion of different compounds into milk. Previous reports have demonstrated that bovine ABCG2 Y581S polymorphism increases fluoroquinolone levels in cow milk. However, the implication of this transporter in the secretion into milk of anti-inflammatory drugs has not yet been studied. The objective of this work was to study the role of ABCG2 in the secretion into milk of flunixin and its main metabolite, 5-hydroxyflunixin, using Abcg2(-/-) mice, and to investigate the implication of the Y581S polymorphism in the secretion of these compounds into cow milk. Correlation with the in vitro situation was assessed by in vitro transport assays using MDCKII cells overexpressing murine and the two variants of the bovine transporter. Our results show that flunixin and 5-hydroxyflunixin are transported by ABCG2 and that this protein is responsible for their secretion into milk. Moreover, the Y581S polymorphism increases flunixin concentration into cow milk, but it does not affect milk secretion of 5-hydroxyflunixin. This result correlates with the differences in the in vitro transport of flunixin between the two bovine variants. These findings are relevant to the therapeutics of anti-inflammatory drugs
    Materia
    Fisiología
    Palabras clave
    Ratones
    Ganado vacuno
    Anti-inflammatory flunixin
    Leche
    ABCG2
    Y581S polymorphism
    URI
    http://hdl.handle.net/10612/9974
    Versión del editor
    http://dmd.aspetjournals.org/content/early/2019/03/11/dmd.118.085506
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