Pharmacokinetic evaluation of the ivermectin-triclabendazole combination in sheep

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

Gent, Bélgica

Congreso; 21st International Conference of the World Association for the Advanced of Veterinary Parasitology; 2007

Drug combinations are now available worldwide to increase the spectrum/efficacy of different anthelmintic preparations. However, information on potential pharmacokinetic interactions occurring after co-administration of different antiparasitic drugs is scarce. The current work was designed to evaluate the pharmacokinetic disposition of ivermectin (IVM) and triclabendazole (TCBZ) given separately or co-administered intravenously to sheep. Fifteen (15) adult female Corriedale sheep (25-30 kg) were randomly allocated into three experimental groups. Animals received either IVM (50 µg/kg) (Group A), triclabendazole (5 mg/kg) (Group B) or IVM (50 µg/kg) + TCBZ (5 mg/kg) (Group C) by intravenous administration. Blood samples were taken between 10 min and 7 days post-treatment.. IVM, TBCZ, TCBZ sulphoxide (TCBZSO) and TCBZ sulphone (TCBZSO2) plasma concentrations were measured by HPLC.. Data was subjected to kinetic and statistical analyses. The IVM plasma disposition was affected by its co-administration with TCBZ. The IVM residence time and elimination half-life were significantly enhanced (between 68 and 83 %) compared to the IVM alone treatment. Additionally, IVM modified the disposition of the TCBZSO metabolite. TCBZSO peak plasma concentration was significantly higher after the co-administration IVM+TCBZ (23.2 ± 3.54µg/ml) in comparison to the TCBZ alone treatment (12.6 ± 2.13µg/ml). The competition between IVM and TCBZ-TCBZSO by the cellular protein transporters (ABC) involved in hepatic and/or intestinal excretion processes may explain the pharmacokinetic interaction observed after their intravenous co-administration. Further research is needed to characterise the involvement of hepatic and intestinal ABC transporters on the disposition and clinical efficacy of these anthelmintic drugs used in combination.