Pharmacologic interaction between oxfendazole and triclabendazole: In vitro biotransformation and systemic exposure in sheep

LIFSCHITZ, A.L.; MATÉ, M.L.; VIRKEL, G.L.; LUQUE, S.E.; CARDOZO, P.A.; LUQUE, S.E.; CARDOZO, P.A.; VIVIANI, P.; LLOBERAS, M.M.; LANUSSE, C.E.; VIVIANI, P.; LLOBERAS, M.M.; LANUSSE, C.E.; LIFSCHITZ, A.L.; MATÉ, M.L.; VIRKEL, G.L.

EXPERIMENTAL PARASITOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2019 vol. 204

0014-4894

The aim of the current work was to evaluate a potential pharmacokinetic interaction between the flukicidetriclabendazole (TCBZ) and the broad-spectrum benzimidazole (BZD) anthelmintic oxfendazole (OFZ) in sheep.To this end, both an in vitro assay in microsomal fractions and an in vivo trial in lambs parasitized withHaemonchus contortus resistant to OFZ and its reduced derivative fenbendazole (FBZ) were carried out. Sheepmicrosomal fractions were incubated together with OFZ, FBZ, TCBZ, or a combination of either FBZ and TCBZ orOFZ and TCBZ. OFZ production was significantly diminished upon coincubation of FBZ and TCBZ, whereasneither FBZ nor OFZ affected the S-oxidation of TCBZ towards its sulfoxide and sulfone metabolites. For the invivo trial, lambs were treated with OFZ (Vermox® oral drench at a single dose of 5 mg/kg PO), TCBZ (Fasinex®oral drench at a single dose of 12 mg/kg PO) or both compounds at a single dose of 5 (Vermox®) and 12 mg/kg(Fasinex®) PO. Blood samples were taken to quantify drug and metabolite concentrations, and pharmacokineticparameters were calculated by means of non-compartmental analysis. Results showed that the pharmacokineticparameters of active molecules and metabolites were not significantly altered upon coadministration. The soleexception was the increase in the mean residence time (MRT) of OFZ and FBZ sulfone upon coadministration,with no significant changes in the remaining pharmacokinetic parameters. This research is a further contributionto the study of metabolic drug-drug interactions that may affect anthelmintic efficacies in ruminants.