Pharmacokinetic profile and anthelmintic efficacy of moxidectin administered by different doses and routes to feedlot calves

Abstract We evaluated the comparative plasma disposition kinetics and efficacy of moxidectin (MXD), administered by the intraruminal (IR) or subcutaneous (SC) route at two different dosage levels (0.2 and 1 mg/kg) in feedlot calves. Additionally, the efficacy was compared to an ivermectin (IVM, SC administration) treated group. This study was divided into two separate studies, the “Pharmacokinetic (PK) study” and the “Efficacy study”. The “PK study” involved 24 calves free of gastrointestinal nematodes (GIN), which were allocated into 4 groups (n = 6) and treated with MXD by either the SC or the IR route at the therapeutic (MXD SC0.2, MXD IR0.2, respectively) or at fivefold the therapeutic dose (MXD SC1.0, MXD IR1.0 , respectively). Blood samples were collected from 3 h up to 14 days post-treatment. MXD concentrations in plasma samples were analyzed by HPLC. The “Efficacy study” included 125 calves naturally infected with GIN, which were allocated into five experimental groups (n = 25 each); the same four MXD-treated groups described for the “PK study”, and an additional group treated by the SC route with IVM (IVM SC0.2 ). The efficacy of IVM given at its therapeutic dose and the different MXD groups at the therapeutic and fivefold the therapeutic dose was calculated by analysis of the individual efficacy using the package eggCounts-2.1-1' on the R software environment, version 3.5.0 ( R Core Team, 2018 ). Daily weight gain (DWG) was also measured over the first 47 days of the fattening cycle. Independently of the administration route, MXD peak plasma concentration (C max ) and area under the concentration-time curve (AUC) were higher in groups treated with the higher dose (1.0 mg/kg), whereas a longer time to reach C max (T max ) was observed after the IR treatments. The observed MXD efficacies were 85% (MXD SC0.2 ), 94% (MXD SC1.0 ), 84% (MXD IR0.2 ) and 99% (MXD IR1.0 ), at day +27. At day +27, all MXD-treated groups showed higher efficacies than the group having received IVM (45%). The post-treatment Cooperia spp. L 3 counts were particularly low in the groups MXD SC1.0 and MXD IR1.0 . All of the groups treated with MXD showed better DWG than the IVM SC0.2 group (P = 0.01). Dose and administration route modifications effectively improved the anthelmintic and productive performance of MXD. A high dose of MXD improved the control of IVM-resistant GIN in feedlot calves. However, this practice must be taken with caution, since MXD resistance could rapidly emerge, especially in grazing cattle.