Eprinomectin B1a

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 5 mg/ml solution (EPRINEX®Multi, Boehringer Ingelheim) administered as a pour-on at 1 mg per kg body weight to lactating dairy goats. The study was conducted in compliance with VICH GCP and anthelmintic efficacy evaluation guidelines and included 20 goats 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 14 days 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 ± 9.7 day*ng/ml and Cmax, 5.35 ± 2.27 ng/ml; individual maximum plasma concentrations were observed from 8 to 48 h after treatment (median Tmax, 0.5 days). 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.

A sensitive and automated method has been developed and validated to determine marker residue eprinomectin B(1a) in bovine milk. Extraction of eprinomectin B(1a) from milk is accomplished with acetonitrile after the addition of an internal standard. The extract containing the analytes is evaporated to dryness and reconstituted in a solution containing 30% 1-N-methylimidazole in acetonitrile. Online derivatization is carried out with trifluoroacetic anhydride. Determination of eprinomectin B(1a) and its internal standard is carried out by HPLC using a reversed-phase C(18) column with a mobile phase consisting of methanol, acetonitrile, water, triethylamine and phosphoric acid. The overall extraction recovery of eprinomectin B(1a) is 94% with milk supplemented between 2 and 50 ng/ml eprinomectin B(1a). Precision RSD averaged 3.0% in Laboratory 1 (n=25) compared to 4.3% in Laboratory 2 (n=35). The limit of quantitation is approximately 2 ng/ml eprinomectin B(1a), the limit of detection is approximately 0.25 ng/ml using this method.

The topical product with three active pharmaceutical ingredients (APIs), namely, esafoxolaner, eprinomectin and praziquantel has demonstrated its efficacy in the treatment of cats with mixed infections with ectoparasites and nematodes and cestodes. A reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed and validated for assay and determination of related substances peaks of three APIs including the assay of antioxidant butylated hydroxytoluene (BHT) in the finished product. Analytes were separated on a short Zorbax SB-C18 column (50 × 4.6 mm I.D., 5 μm particle size, pore size: 80 Å) with gradient elution at 40 °C column temperature. Analytes were detected at 245 nm for praziquantel, esafoxolaner, eprinomectin and their degradation products. BHT and eprinomectin degradation product 8a-oxo-B1a were detected at 280 nm. All analytes of interest were adequately separated within 40 min. The assay for praziquantel, esafoxolaner, eprinomectin and BHT was conducted against their corresponding external reference standards. The related substances peaks of each API were determined by peak area and relative response factor against total peak area of their corresponding API peak in sample solution. This method has been demonstrated to be accurate, robust, specific and stability indicating.