Pharmacokinetics of Moxidectin in Bare-Nosed Wombats (Vombatus ursinus) After Intravenous, Sub-Cutaneous and Transdermal Administration

IF 1.4 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY
E. K. Stott, L. F. Skerratt, T. Whittem, M. Leeming, K. Pillay, G. S. Doran, B. Gardner, M. Lynch, M. Klein, P. Holz, T. Chen, J. Hufschmid, A. P. Woodward
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Abstract

The anti-parasitic drug moxidectin is a frontline treatment for sarcoptic mange in bare-nosed wombats (Vombatus ursinus), a disease causing significant animal welfare issues and instances of local population declines. Despite widespread usage, knowledge of species-specific pharmacokinetics of moxidectin in bare-nosed wombats is still limited. This study describes the clinical pharmacokinetics of moxidectin by intravenous, subcutaneous, and transdermal routes of administration in bare-nosed wombats. Plasma moxidectin concentration was assessed by liquid chromatography mass spectrometry and analysed by Bayesian hierarchical modelling. Plasma clearance was 1.11–1.85 mL/min/kg. The subcutaneous route showed biphasic absorption, dominated by a slow terminal absorption phase (80% of the effective dose of moxidectin was absorbed in this phase) with a half-life of approximately 631 h (26.3 days). The transdermal route had an estimated half-life of 21.78 h (1308) min. The average bioavailability was 0.59% and 95.7% by the transdermal and subcutaneous route, respectively. This detailed insight into the pharmacokinetics of moxidectin in bare-nosed wombats provides a crucial foundation for the design of treatment regimens, whilst also highlighting the inefficiency of transdermal delivery.

莫西丁素在裸鼻袋熊(Vombatus ursinus)静脉、皮下和透皮给药后的药动学。
抗寄生虫药物莫西菌素是治疗裸鼻袋熊(Vombatus ursinus)疥癣病的一线药物,这种疾病会导致严重的动物福利问题和当地种群数量下降。尽管莫西丁在裸鼻袋熊体内被广泛使用,但对其物种特异性药代动力学的了解仍然有限。本研究描述了莫西菌素在裸鼻袋熊体内经静脉、皮下和透皮给药的临床药代动力学。用液相色谱-质谱法测定血浆莫西丁素浓度,并用贝叶斯分层模型进行分析。血浆清除率为1.11 ~ 1.85 mL/min/kg。皮下吸收为双相吸收,以缓慢的末期吸收为主(莫西菌素有效剂量的80%在此期被吸收),半衰期约为631 h(26.3天)。经皮途径估计半衰期为21.78 h (1308) min。经皮途径和皮下途径的平均生物利用度分别为0.59%和95.7%。这项对莫西丁在裸鼻袋熊体内药代动力学的详细研究为治疗方案的设计提供了重要的基础,同时也强调了透皮给药的低效率。
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来源期刊
CiteScore
3.10
自引率
15.40%
发文量
69
审稿时长
8-16 weeks
期刊介绍: The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.
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