Table_1_Fecal elimination of fluralaner in different carnivore species after oral administration.docx

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.

氟雷拉纳（Fluralaner）是一款新兴的外用寄生虫驱除药，亦是异恶唑啉类杀虫剂（isoxazoline parasiticides）这一全新药物类别中的首款成员。它被广泛应用于伴侣动物领域，不仅因其驱虫谱广泛（可杀灭跳蚤、蜱虫及其他螨类），还因其使用便捷——单次口服给药即可维持1至3个月的药效。已知该药物主要以原型化合物形式通过粪便排出，排泄占比超过90%。对于动物园食肉动物而言，体外寄生虫防控同样至关重要，但目前尚无获批上市的专用防控产品。本研究的首要目标为评估氟雷拉纳在动物园食肉动物体内的药代动力学特征；第二目标则是验证氟雷拉纳能否在较长时间内被机体排泄，进而引发其对节肢动物等非靶标物种存在潜在影响的相关疑问。研究人员通过异速生长方程调整口服给药剂量后，对受试动物进行给药，并在长达3个月的周期内定期收集粪便样本，以此绘制氟雷拉纳的粪便排泄曲线，作为血浆药代动力学的替代指标（出于伦理与安全考量，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（LC-MSMS）技术进行分析。研究结果显示，尽管存在样本量有限等局限性，但大多数食肉动物的粪便中可检出氟雷拉纳达数周至数月不等（狮子在给药后89天仍可检测到氟雷拉纳）。据我们所知，本研究首次证实了动物体内存在如此漫长的药物排泄周期。考虑到该类化合物的广泛使用，未来仍需开展进一步研究，以评估食肉动物粪便中存在的活性残留对环境，尤其是犬、猫等动物所带来的相关风险。