RT info:eu-repo/semantics/preprint
T1 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
A1 García Mateos, Dafne
A1 Garcia-Lino, Alba Maria
A1 Alvarez-Fernandez, Indira
A1 Blanco Paniagua, Esther
A1 Fuente, Álvaro de la
A1 Álvarez de Felipe, Ana Isabel
A1 Merino Peláez, Gracia
A2 Fisiologia
K1 Fisiología
K1 Ratones
K1 Ganado vacuno
K1 Anti-inflammatory flunixin
K1 Leche
K1 ABCG2
K1 Y581S polymorphism
AB Flunixin meglumine is a nonsteroidal anti-inflammatory drug (NSAID) widely used inveterinary medicine. It is indicated to treat inflammatory processes, pain and pyrexia in farmanimals. In addition, it is one of the few NSAIDs approved for use in dairy cows, andconsequently gives rise to concern regarding its milk residues. The ABCG2 efflux transporter isinduced during lactation in the mammary gland and plays an important role in the secretion ofdifferent compounds into milk. Previous reports have demonstrated that bovine ABCG2 Y581Spolymorphism increases fluoroquinolone levels in cow milk. However, the implication of thistransporter in the secretion into milk of anti-inflammatory drugs has not yet been studied. Theobjective of this work was to study the role of ABCG2 in the secretion into milk of flunixin andits main metabolite, 5-hydroxyflunixin, using Abcg2(-/-) mice, and to investigate the implicationof the Y581S polymorphism in the secretion of these compounds into cow milk. Correlationwith the in vitro situation was assessed by in vitro transport assays using MDCKII cellsoverexpressing murine and the two variants of the bovine transporter. Our results show thatflunixin and 5-hydroxyflunixin are transported by ABCG2 and that this protein is responsiblefor their secretion into milk. Moreover, the Y581S polymorphism increases flunixinconcentration into cow milk, but it does not affect milk secretion of 5-hydroxyflunixin. Thisresult correlates with the differences in the in vitro transport of flunixin between the two bovinevariants. These findings are relevant to the therapeutics of anti-inflammatory drugs
PB ASPET
YR 2019
FD 2019-03-18
LK http://hdl.handle.net/10612/9974
UL http://hdl.handle.net/10612/9974
NO Drug Metabolism and Disposition
NO 35 p.
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 05-jun-2024