2024-03-28T18:15:58Zhttp://buleria.unileon.es/oai/requestoai:buleria.unileon.es:10612/99742023-06-01T07:05:09Zcom_10612_17col_10612_18
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
García Mateos, Dafne
Garcia-Lino, Alba Maria
Alvarez-Fernandez, Indira
Blanco-Paniagua, Esther
Fuente, Álvaro de la
Álvarez de Felipe, Ana Isabel
Merino Peláez, Gracia
Fisiologia
Fisiología
35 p.
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
2019-03-18
2019-03-18
2019-03-18
info:eu-repo/semantics/preprint
Drug Metabolism and Disposition
http://dmd.aspetjournals.org/content/early/2019/03/11/dmd.118.085506
http://hdl.handle.net/10612/9974
info:eu-repo/semantics/openAccess
ASPET