Ivermectin and abamectin interaction: pharmacokinetic-pharmacodynamic assessment in Cooperia spp. infected calves.

LIFSCHITZ, A.; FIEL, C.; DOMINGUEZ, P.; VIRKEL, G.; CANTÓN, C.; LANUSSE, C.; BALLENT, M.

Liverpool

Congreso; 25º Conference of the World Association for the Advancement of Veterinary Parasitology WAAVP; 2015

Drug combined formulations are available as pharmacological tools designed to enhanceanthelmintic efficacy and to delay the development of resistance. However, the in vivopharmacological consequences emerging from the co-administration of anthelmintic moleculesshould be deeply evaluated in the early stages of combined formulations development. Thecurrent work investigated the pharmacokinetic-pharmacodynamic interaction ocurring after theco-administration of ivermectin (IVM) and abamectin (ABM) to parasitised calves. Theexperimental trial was performed in two phases. In Phase I, twenty four (24) Aberdeen Angus-Hereford cross-breed calves experimentally infected with an IVM susceptible strain of Cooperiaspp. were subcutaneously treated with IVM (0.1 mg/kg), ABM (0.1 mg/kg) or IVM+ABM (0.05mg/kg of each compound). In Phase II, thirty two (32) calves naturally infected with an IVMresistant strain of Cooperia spp received the same treatments than in Phase I but at thetherapeutic dose rate of 0.2 mg/kg. Blood samples were taken up to 21 days post-treatment tomeasure macrocyclic lactones (ML) concentrations by HPLC. The indirect estimation of efficacywas performed by faecal egg count reduction test (FECRT). In calves infected with resistantnematodes, a higher faecal eggs reduction was obtained after the IVM+ABM administration (89%) compared to the ABM (76.9 %) and IVM (55 %) single treatments. Similar tendency wasobserved in calves infected with susceptible Cooperia spp. but treated with 50% of thetherapeutic dose rate. The ML plasma concentrations were between 1.66 and 4.38- fold higherduring the elimination phase (13-20 days post-administration) in the co-administered animals.The systemic exposure (measured as AUC) during this time period was 38 % (IVM) and 60 %(ABM) greater in the calves receiving the combined treatment. The improved performanceobserved after the co-administration of IVM and ABM may be based on drug to drug