Boehringer Ingelheim Vetmedica GmbH, Kathrinenhof Research Center, Rohrdorf, Germany.
Boehringer Ingelheim Animal Health USA, Inc., North Brunswick, NJ, USA.
J Vet Pharmacol Ther. 2021 Nov;44(6):952-960. doi: 10.1111/jvp.13008. Epub 2021 Sep 20.
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: AUC , 23.8 ± 9.7 day*ng/ml and C , 5.35 ± 2.27 ng/ml; individual maximum plasma concentrations were observed from 8 to 48 h after treatment (median T , 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.
哺乳被认为是一种生理协变量，可能会影响全身作用药物（包括大环内酯类）的暴露特征，并可能改变其药理反应。本研究首次在同一研究中对泌乳奶山羊按 1mg/kg 体重进行浇泼给药的伊维菌素 5mg/ml 溶液（Boehringer Ingelheim 的 EPRINEX Multi）的血浆水平和治疗驱虫效果进行了特征描述。该研究是按照 VICH GCP 和驱虫药疗效评估指南进行的，包括 20 只患有诱导性成年胃肠道和肺线虫感染的奶山羊。这些山羊根据治疗前的体重进行分组，并随机分为不治疗（对照）或伊维菌素治疗两组。在动物进行剖检以进行寄生虫计数和鉴定时，在治疗后最多 14 天内每隔一段时间采集血浆样本，以确定伊维菌素（B1a 成分）的血浆处置动力学。在 10 只接受伊维菌素治疗的山羊中确定的伊维菌素基本药代动力学参数如下：AUC ，23.8±9.7 天*ng/ml 和 C ，5.35±2.27ng/ml；个体最大血浆浓度在治疗后 8 至 48 小时（中位数 T ，0.5 天）观察到。与未处理的对照组相比，伊维菌素治疗动物的蠕虫负荷显著（p<.01）降低，表明伊维菌素的局部治疗效果≥97%至 100%，可有效对抗成年捻转血矛线虫、奥斯特线虫、网尾线虫、细颈线虫、胎生网尾线虫、马副蛔虫、库蠓属线虫、捻转血矛线虫和食道口线虫。泌乳奶山羊的药代动力学参数和驱虫活性与接受伊维菌素浇泼治疗的已感染的幼龄生长和成年非泌乳奶山羊相似。
