Pharmacokinetic-pharmacodynamic relationships of pour-on administered eprinomectin in nematode-infected lactating female and male castrated dairy breed goats

Abstract

Eprinomectin (EPM), a macrocyclic lactone with low excretion in milk and high efficacy against endoparasites and ectoparasites, is widely used in veterinary medicine. In this paper, EPM pharmacokinetics and anthelmintic efficacy previously established in one study with lactating female goats and three studies with male castrated growing dairy breed goats (all with induced mixed adult gastrointestinal nematode parasitism and treated with a single 1-mg/kg pour-on administration of EPM) were retrospectively evaluated using pharmacokinetic-pharmacodynamic (PK-PD) modeling. The PK-PD analyses between EPM exposure (Cmax and AUClast) and anthelmintic response (percent efficacy) were performed for lactating female goats only and pooled lactating female and male castrated goats. The Cmax and AUClast showed no significant difference between lactating female goats and combined male castrated goats. PK-PD modeling demonstrated Trichostrongylus colubriformis, a small-intestine nematode, as a suitable indicator of the EPM nematocidal efficacy. The EC90 values obtained by modeling Cmax vs T. colubriformis were 3.50 and 2.43 ng/mL for lactating female goats only and pooled lactating female and male castrated goats, respectively. The values of AUClast needed for 90% efficacy of T. colubriformis were 25.4 and 21.1 day*ng/mL for lactating female goats only and pooled lactating female and male castrated goats, respectively. Overall, the predicted pharmacological response against T. colubriformis is similar for lactating goats only and pooled lactating female and male castrated goats and correlates with observed efficacy. In conclusion, a dosage of 1-mg/kg EPM as a pour-on is sufficient to ensure efficacy against common nematodes in both lactating female and male castrated goats.