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口服给药后不同食肉动物物种中氟拉那韦的粪便排泄情况。

Fecal elimination of fluralaner in different carnivore species after oral administration.

作者信息

Berny Philippe Jacques, Belhadj Dalil, España Bernadette, Lécu Alexis

机构信息

UR-ICE Vetagro Sup, Lyon, France.

Muséum National d'Histoire Naturelle, Paris, France.

出版信息

Front Vet Sci. 2024 Aug 16;11:1279844. doi: 10.3389/fvets.2024.1279844. eCollection 2024.

DOI:10.3389/fvets.2024.1279844
PMID:39220768
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11362066/
Abstract

Fluralaner is a recent external parasiticide, first of a new class of drugs (isoxazoline parasiticides). It is widely used in companion animals both for its wide spectrum (fleas, ticks and other mites) but also for its ease of use (oral tablets given once for 1 to three months). It is known to be eliminated primarily via the feces (>90%) as the unchanged compound. In zoo carnivores, controlling external parasites is also important and there are no specific products with a marketing authorization to control them. The first objective of this study was to evaluate the pharmacokinetic profile of fluralaner in zoo carnivores. The second objective was to demonstrate that fluralaner can be eliminated over a prolonged period of time, thereby raising questions about its potential impact on non-target species such as arthropods. After adjusting the oral dose using allometric equations, animals were dosed and fecal samples were collected on a regular basis for up to three months to determine the fecal elimination curve of fluralaner as a surrogate of plasma kinetics (for ethical and safety reasons, plasma samples were not considered). All samples were analyzed with a validated LC-MSMS technique. Our results show that, despite limitations and a limited number of animals included, most carnivores eliminate fluralaner in their feces for several weeks to months (in Lions, fluralaner was still detectable after 89 days). To our knowledge, this is the first study demonstrating such a long elimination period in animals. Further studies would be required to investigate the risk associated with the presence of active residues in other carnivore feces for the environment, especially in dogs and cats, considering the large use of this class of compounds.

摘要

氟虫腈是一种新型的体外驱虫药,属于一类新型药物(异恶唑啉类驱虫药)中的第一种。它因其广泛的杀虫谱(跳蚤、蜱虫和其他螨虫)以及使用方便(口服片剂,每1至3个月服用一次)而广泛应用于伴侣动物。已知它主要通过粪便(>90%)以未改变的化合物形式排出体外。在动物园食肉动物中,控制体外寄生虫也很重要,但目前没有获得上市许可的专门用于控制它们的产品。本研究的首要目标是评估氟虫腈在动物园食肉动物中的药代动力学特征。第二个目标是证明氟虫腈可以在较长时间内排出体外,从而引发关于其对节肢动物等非目标物种潜在影响的问题。使用异速生长方程调整口服剂量后,给动物给药,并定期收集粪便样本,长达三个月,以确定氟虫腈的粪便排泄曲线,作为血浆动力学的替代指标(出于伦理和安全原因,未采集血浆样本)。所有样本均采用经过验证的液相色谱 - 串联质谱技术进行分析。我们的结果表明,尽管存在局限性且纳入的动物数量有限,但大多数食肉动物在数周甚至数月内通过粪便排出氟虫腈(在狮子体内,89天后仍可检测到氟虫腈)。据我们所知,这是第一项证明动物体内存在如此长排泄期的研究。考虑到这类化合物的大量使用,需要进一步研究调查其他食肉动物粪便中活性残留物对环境的风险,尤其是对犬类和猫类的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab4d/11362066/1e77d1c0aecf/fvets-11-1279844-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab4d/11362066/fb71fba0005f/fvets-11-1279844-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab4d/11362066/68b594f27371/fvets-11-1279844-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab4d/11362066/1e77d1c0aecf/fvets-11-1279844-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab4d/11362066/fb71fba0005f/fvets-11-1279844-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab4d/11362066/68b594f27371/fvets-11-1279844-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab4d/11362066/1e77d1c0aecf/fvets-11-1279844-g003.jpg

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Scientific Opinion of the Scientific Panel on Plant Protection Products and their Residues (PPR Panel) on testing and interpretation of comparative metabolism studies.
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