RT info:eu-repo/semantics/preprint
T1 Role of eprinomectin as inhibitor of the ruminant ABCG2 transporter: Effects on plasma distribution of danofloxacin and meloxicam in sheep
A1 Garcia-Lino, Alba M.
A1 Garcia-Mateos, Dafne
A1 Alvarez-Fernandez, Indira
A1 Blanco Paniagua, Esther
A1 Medina, Juan M.
A1 Merino Peláez, Gracia
A1 Álvarez de Felipe, Ana Isabel
A2 Otros
K1 Sanidad animal
K1 ABCG2
K1 Danofloxacin
K1 Eprinomectin
K1 Macrocyclic lactone
K1 Meloxicam
K1 Sheep
AB Therapeutic outcome results of the coadministration of several drugs in veterinary medicine is affected by, among others, the relationship between drugs and ATP-binding cassette (ABC) transporters, such as ABCG2. ABCG2 is an efflux protein involved in the bioavailability and milk secretion of drugs. The aim of this work was to determine the role of eprinomectin, a macrocyclic lactone (ML) member of avermectin class, as inhibitor of ABCG2. The experiments were carried out through in vitro inhibition assays based on mitoxantrone accumulation and transport assays in ovine ABCG2 transduced cells using the antimicrobial drug danofloxacin and the anti-inflammatory drug meloxicam, both widely used in veterinary medicine and well known ABCG2 substrates. The inhibition results obtained showed that eprinomectin was an efficient in vitro ABCG2 inhibitor, tested in mitoxantrone accumulation assays. In addition, this ML decreased ovine ABCG2-mediated transport of danofloxacin and meloxicam. To evaluate the role of eprinomectin in systemic exposure of drugs, pharmacokinetic assays based on subcutaneous coadministration of eprinomectin with danofloxacin (1.25 mg/kg) or meloxicam (0.5 mg/kg) in sheep were performed obtaining a significant increase of systemic exposure of these drugs. Especially relevant was the increase of the systemic concentration of meloxicam, since coadministration with eprinomectin increased significantly the plasma concentration of meloxicam, obtaining an increase of AUC (0-72 h) value of more than 40%.
PB Elsevier
SN 0034-5288
LK http://hdl.handle.net/10612/13314
UL http://hdl.handle.net/10612/13314
NO 6 p.
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 20-abr-2024