Monepantel in cattle: pharmacokinetics and nematodicidal efficacy

CANTÓN, CANDELA; CANTÓN, LUCILA; LIFSCHITZ, ADRIÁN LUIS; DOMINGUEZ, PAULA; TORRES, JUAN; LANUSSE, CARLOS EDMUNDO; ALVAREZ, LUIS IGNACIO; CEBALLOS, LAURA; BALLENT, MARIANA

Utah

Congreso; AAVP 65th Annual Conference; 2020

American Association of Veterinary Parasitologists

The increasing levels of resistance to all traditional anthelmintic classes have encouraged thesearch for molecules with alternative mechanisms of action. The broad-spectrum nematodicidaldrug Monepantel (MNP) was initially developed to use in sheep. The goals of the work describedhere were to evaluate the pharmacokinetic (PK) behaviour and anthelmintic efficacy of MNPgiven to calves naturally infected with gastrointestinal nematodes (GIN) resistant to ivermectin(IVM) on two commercial farms. Thirty (30) male calves were randomly allocated into twogroups (n= 15) and treated with either MNP orally at 2.5 mg/kg or IVM subcutaneously at 0.2mg/kg. Eight animals from the MNP treated group (Farm 1) were randomly selected to performthe PK study. Drug concentrations were measured by HPLC. The efficacy was determined at 15days after treatment by the FECRT. MNP and MNPSO2 were the main analytes recovered inplasma. MNPSO2 (measured in plasma up to 216 h post-treatment) systemic exposure wasmarkedly higher compared to that obtained for MNP (measured up to 120 h post-treatment).Higher Cmax and AUC values were obtained for the active MNPSO2 metabolite (96.8 ±29.7ng/mL and 9220 ± 1720ng.h/mL, respectively) compared to MNP (21.5 ± 4.62ng/mL and1709 ± 651ng.h/mL, respectively). The MNPSO2 AUC value was 6-fold higher compared to theparent drug. Efficacies of 99% (Farm 1) and 96% (Farm 2) demonstrated the high efficacy ofMNP (P< 0.05) against GIN resistant to IVM in cattle (reductions between 43 and 68% in bothfarms). While IVM failed to control Haemonchus spp. and Cooperia spp., MNP achieved 100%efficacy against Haemonchus spp., Cooperia spp. and Ostertagia spp. on both farms. However,MNP failed to control Oesophagostomum spp. (efficacies ranging from 22 to 74%). Inconclusion, the oral treatment with MNP should be considered for dealing with IVM resistantparasites in cattle.