Abstract

Lactation is discussed as a physiological covariate which may influence the exposure characteristics of systemically acting drugs including macrocyclic lactones and potentially alter their pharmacological response. This study characterizes for the first time in the same study, the plasma profile and therapeutic anthelmintic efficacy of eprinomectin 5mg/ml solution (EPRINEX® Multi, Boehringer Ingelheim) administered as a pour-on at 1mg per kg body weight to lactating dairy goats. The study was conducted in compliance with VICH GCP and anthelmintic efficacy evaluation guidelines and included 20goats harboring induced adult gastrointestinal and pulmonary nematode infections. The goats were blocked on pre-treatment body weight and randomly allocated either to remain untreated (control) or to be eprinomectin-treated. Plasma samples to determine the plasma disposition kinetics of eprinomectin (B1a component) were obtained at intervals up to 14days following treatment when the animals were necropsied for parasite enumeration and identification. Basic pharmacokinetic parameters of eprinomectin determined in the ten eprinomectin-treated goats were as follows: AUClast , 23.8±9.7day*ng/ml and Cmax , 5.35±2.27ng/ml; individual maximum plasma concentrations were observed from 8 to 48h after treatment (median Tmax , 0.5days). Topical eprinomectin treatment efficacy, based on significant (p<.01) worm burden reductions in eprinomectin-treated animals relative to untreated controls, was ≥97% to 100% against adult Dictyocaulus filaria, Haemonchus contortus, Teladorsagia circumcincta(pinnata/trifurcata), Trichostrongylus axei, T.colubriformis, Cooperia curticei, Nematodirus battus, and Oesophagostomum venulosum. Both pharmacokinetic parameters and anthelmintic activity in lactating dairy goats were similar to those observed in parasitized young growing and adult female non-lactating dairy goats treated with eprinomectin administered as a pour-on.

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