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Título
Coadministration of ivermectin and abamectin affects milk pharmacokinetics of the antiparasitic clorsulon in Assaf sheep
Autor
Facultad/Centro
Área de conocimiento
Título de la revista
Frontiers in Veterinary Science
Cita Bibliográfica
Blanco-Paniagua, E., Álvarez-Fernández, L., Millán-García, A., Rivas, G., Álvarez, A. I., & Merino, G. (2023). Coadministration of ivermectin and abamectin affects milk pharmacokinetics of the antiparasitic clorsulon in Assaf sheep. Frontiers in veterinary science, 10. https://doi.org/10.3389/fvets.2023.1268658
Editorial
Frontiers
Fecha
2023
Resumen
[EN] In veterinary field, drug exposure during milk production in dairy cattle is considered
a major health problem which concerns dairy consumers. The induced expression
of the ABC transporter G2 (ABCG2) in the mammary gland during lactation plays
a significant role in the active secretion of many compounds into milk. The
main objective of this study was to determine the involvement of ABCG2 in the
secretion into milk of the antiparasitic clorsulon in sheep as well as the possible
effect of the coadministration of model ABCG2 inhibitors such as macrocyclic
lactones on this process. Cells transduced with the ovine variant of ABCG2 were
used to carry out in vitro transepithelial transport assays in which we showed
that clorsulon is a substrate of the ovine transporter. In addition, ivermectin and
abamectin significantly inhibited clorsulon transport mediated by ovine ABCG2. In
vivo interactions were studied in Assaf sheep after coadministration of clorsulon
(in DMSO, 2 mg/kg, s.c.) with ivermectin (Ivomec®, 0.2 mg/kg, s.c.) or abamectin
(in DMSO, 0.2 mg/kg, s.c.). After ivermectin and abamectin treatment, no relevant
statistically significant differences in plasma levels of clorsulon were reported
between the experimental groups since there were no differences in the area
under the plasma concentration-curve (AUC) between clorsulon treatment alone
and coadministration with macrocyclic lactones. With regard to milk, total amount
of clorsulon, as percentage of dose excreted, did not show statistically significant
differences when macrocyclic lactones were coadministered. However, the
AUC for clorsulon significantly decreased (p < 0.05) after coadministration with
ivermectin (15.15 ± 3.17 μg h/mL) and abamectin (15.30 ± 3.25 μg h/mL) compared
to control group (20.73 ± 4.97 μg h/mL). Moreover, milk parameters such as half-
life (T1/2) and mean residence time (MRT) were significantly lower (p < 0.05) after
coadministration of macrocyclic lactones. This research shows that the milk
pharmacokinetics of clorsulon is affected by the coadministration of ABCG2
inhibitors, reducing drug persistence in milk.
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ID proyecto
- info:eu-repo/grantAgreement/AEI/Programa Estatal de I+D+i Orientada a los Retos de la Sociedad/RTI2018-100903-B-I00/ES/PAPEL DEL TRANSPORTADOR ABCG2 Y SUS POLIMORFISMOS EN LA EXCRECION DE AGENTES ANTIPARASITARIOS Y PESTICIDAS EN LECHE DE RUMIANTES
- info:eu-repo/grantAgreement/AEI/PID2021-125660OB-I00
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