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氟虫腈在树袋熊体内的药代动力学及安全性

Pharmacokinetics and safety of topical fluralaner in koalas .

作者信息

Young Ellyssia T, McKelson Jessica, Kalstrom Daniel, Sipthorp Lachlan, Wicker Leanne, Higgins Damien, Marschner Caroline, Nichols David S, Phalen David, Greenville Aaron C, Carver Scott

机构信息

School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.

Phillip Island Nature Park, Cowes, Victoria, Australia.

出版信息

Int J Parasitol Parasites Wildl. 2024 Sep 24;25:100999. doi: 10.1016/j.ijppaw.2024.100999. eCollection 2024 Dec.

Abstract

Sarcoptic mange (etiological agent ) is among the most important parasitic diseases of some marsupial species and has been an emerging disease of koalas, causing welfare and conservation implications. Fluralaner (Bravecto® MSD Animal Health), an ectoparasiticide of the isoxazoline class, has been demonstrated as a long-lasting and efficacious chemotherapeutic agent against sarcoptic mange in multiple mammal species and may also be beneficial for impacted koalas. Here, we evaluated the pharmacokinetics and clinical safety of fluralaner in koalas. Healthy captive individuals were treated topically with 85 mg/kg fluralaner administered to the interscapular epidermis. Following treatment, fluralaner was detected in plasma using ultra-performance liquid chromatography and tandem mass-spectrometry over a 12-week period. The mean maximum plasma concentration (C) was 66.4 ng/mL; mean time was C of 2.71 days; plasma elimination half-life (T) was 30.91 days; and mean residence time (MRT) was 27.38 days. Haematological, blood biochemical, animal husbandry and clinical observations, over the same time period, demonstrated fluralaner was well tolerated. Overall, this research suggests fluralaner is a safe and long-lasting chemotherapeutic agent that may be efficacious against in koalas. Further research focussed on quantifying efficacy in captive and field settings, and across a range of disease severities would be valuable.

摘要

疥螨病(病原体)是一些有袋类物种最重要的寄生虫病之一,并且一直是考拉的一种新出现疾病,对其福利和保护产生影响。氟雷拉纳(拜宠爽®,默克动物保健公司)是一种异恶唑啉类体外寄生虫杀虫剂,已被证明是一种对多种哺乳动物物种的疥螨病具有长效且有效的化学治疗剂,对受影响的考拉可能也有益处。在此,我们评估了氟雷拉纳在考拉体内的药代动力学和临床安全性。对健康的圈养考拉个体在肩胛间表皮局部给予85毫克/千克的氟雷拉纳。治疗后,在12周的时间内使用超高效液相色谱和串联质谱法在血浆中检测到氟雷拉纳。平均最大血浆浓度(Cmax)为66.4纳克/毫升;达峰时间(Tmax)为2.71天;血浆消除半衰期(t1/2)为30.91天;平均驻留时间(MRT)为27.38天。在同一时期进行的血液学、血液生化、饲养管理和临床观察表明,考拉对氟雷拉纳耐受性良好。总体而言,这项研究表明氟雷拉纳是一种安全且长效的化学治疗剂,可能对考拉的疥螨病有效。进一步针对圈养和野外环境以及一系列疾病严重程度进行疗效量化的研究将很有价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a141/11993836/006071fa497b/ga1.jpg

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