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氟拉那(博来恩™)和伊维菌素同时给药后犬的血浆药代动力学特征

Plasma pharmacokinetic profile of fluralaner (Bravecto™) and ivermectin following concurrent administration to dogs.

作者信息

Walther Feli M, Allan Mark J, Roepke Rainer K A

机构信息

Merck Animal Health, 2 Giralda Farms, Madison, NJ, USA.

MSD Animal Health Innovation GmbH, Zur Propstei, 55270, Schwabenheim, Germany.

出版信息

Parasit Vectors. 2015 Oct 6;8:508. doi: 10.1186/s13071-015-1123-8.

Abstract

BACKGROUND

Fluralaner is a novel systemic ectoparasiticide for dogs providing immediate and persistent flea, tick and mite control after a single oral dose. Ivermectin has been used in dogs for heartworm prevention and at off label doses for mite and worm infestations. Ivermectin pharmacokinetics can be influenced by substances affecting the p-glycoprotein transporter, potentially increasing the risk of ivermectin neurotoxicity. This study investigated ivermectin blood plasma pharmacokinetics following concurrent administration with fluralaner.

FINDINGS

Ten Beagle dogs each received a single oral administration of either 56 mg fluralaner (Bravecto™), 0.3 mg ivermectin or 56 mg fluralaner plus 0.3 mg ivermectin/kg body weight. Blood plasma samples were collected at multiple post-treatment time points over a 12-week period for fluralaner and ivermectin plasma concentration analysis. Ivermectin blood plasma concentration profile and pharmacokinetic parameters Cmax, tmax, AUC∞ and t½ were similar in dogs administered ivermectin only and in dogs administered ivermectin concurrently with fluralaner, and the same was true for fluralaner pharmacokinetic parameters.

CONCLUSIONS

Concurrent administration of fluralaner and ivermectin does not alter the pharmacokinetics of either compound. Based on the plasma pharmacokinetic profile and the clinical observations, there is no evident interaction between fluralaner and ivermectin, and co-administration does not increase the risk of ivermectin associated neurotoxicity.

摘要

背景

氟虫腈是一种新型的犬用全身性外寄生虫杀虫剂,单次口服给药后可立即且持续地控制跳蚤、蜱虫和螨虫。伊维菌素已用于犬类预防心丝虫,并以非标签剂量用于治疗螨虫和蠕虫感染。伊维菌素的药代动力学可能会受到影响P-糖蛋白转运体的物质的影响,从而可能增加伊维菌素神经毒性的风险。本研究调查了氟虫腈与伊维菌素同时给药后的伊维菌素血浆药代动力学。

研究结果

十只比格犬分别接受单次口服56毫克氟虫腈(拜宠清™)、0.3毫克伊维菌素或56毫克氟虫腈加0.3毫克伊维菌素/千克体重。在12周的多个治疗后时间点采集血浆样本,用于分析氟虫腈和伊维菌素的血浆浓度。仅接受伊维菌素治疗的犬和同时接受氟虫腈与伊维菌素治疗的犬的伊维菌素血浆浓度曲线及药代动力学参数Cmax、tmax、AUC∞和t½相似,氟虫腈的药代动力学参数也是如此。

结论

氟虫腈和伊维菌素同时给药不会改变任何一种化合物的药代动力学。基于血浆药代动力学特征和临床观察,氟虫腈和伊维菌素之间没有明显的相互作用,联合给药不会增加伊维菌素相关神经毒性的风险。

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