Monepantel-based anthelmintic combinations to optimize parasite control in cattle

Improvement in the use of existing anthelmintics is a high priority need for the pharmaco-parasitology research field, considering the magnitude and severity of anthelmintic resistance as an important issue in livestock production. In the work described here, monepantel (MNP) was given alone or co-administered with either macrocyclic lactone (ML) or benzimidazole (BZ) anthelmintics to calves naturally infected with ML- and BZ-resistant gastrointestinal (GI) nematodes on two different commercial cattle farms. Both pharmacokinetic (PK) and efficacy assessments were performed. On Farm A, male calves (n = 15 per group) were treated with either MNP orally (2.5 mg/kg), IVM s.c. (0.2 mg/kg), ricobendazole (RBZ) s.c. (3.75 mg/kg) or remained untreated. On Farm B, eight groups (n = 15) of male calves received treatment with either: MNP, abamectin (ABM, oral, 0.2 mg/kg), RBZ (s.c., 3.75 mg/kg), albendazole (ABZ, oral, 5 mg/kg), MNP+ABM, MNP+RBZ, MNP+ABZ (all at the above-mentioned routes and doses) or remained untreated. Seven animals from each treated group (Farm B) were randomly selected to perform the PK study. MNP and its metabolite monepantel sulphone (MNPSO₂) were the main analytes recovered in plasma after HPLC analysis. The combined treatments resulted in decreased systemic exposures to MNP parent drug compared with that observed after treatment with MNP alone (P < 0.05). However, the systemic availability of the main MNP metabolite (MNPSO₂) was unaffected by co-administration with either ABM, RBZ or ABZ. Efficacies of 98% (Farm A) and 99% (Farm B) demonstrated the high efficacy of MNP given alone (P < 0.05) against GI nematodes resistant to ML and BZ in cattle. While the ML (IVM, ABM) failed to control Haemonchus spp., Cooperia spp. and Ostertagia spp., MNP achieved 99% to 100% efficacy against those nematode species on both commercial farms. However, MNP alone failed to control Oesophagostomum spp. (60% efficacy) on Farm A. The co-administered treatments MNP+ABZ and MNP+RBZ reached a 100% reduction against all GI nematode genera. In conclusion, the oral treatment with MNP should be considered to deal with resistant nematode parasites in cattle. The use of MNP in combination with BZ compounds could be a valid strategy to extend its lifespan for use in cattle as well as to reverse its poor activity against Oesophagostomum spp.