Combined use of ivermectin and triclabendazole in sheep –in vitro and in vivo characterization of their pharmacological interaction-

LIFSCHITZ, A.; VIRKEL, G.; BALLENT, M.; SALLOVITZ, J.; LANUSSE, C.

The Veterinary Journal

Elsevier

Año: 2009 p. 261 - 268

1090-0233

Abstract The current work was addressed to evaluate the pharmacokinetic disposition of ivermectin (IVM) and triclabendazole (TCBZ) given either separately or co-administered to sheep. Corriedale sheep received either IVM alone, TCBZ alone or IVM+TCBZ by intravenous administration. IVM elimination was delayed with plasma availability 3-fold higher in the presence of TCBZ. The plasma disposition of TCBZ and its metabolites was also affected after its intravenous co-administration with IVM. Higher peak plasma concentrations (Cmax) were observed for the TCBZ metabolites after the co-administration of TCBZ+IVM compared to those obtained after the TCBZ alone treatment. Complementary in-vitro assays were carried out to assess the influence of TCBZ on the P-glycoprotein-mediated intestinal transport of IVM, using the everted gut sac technique. An enhanced IVM accumulation in the intestinal wall was measured after its co-incubation with TCBZ. The molecular basis and the therapeutic impact of this kinetic interaction are under further assessment in our laboratory.