Abstract

As a typical and broad-spectrum benzimidazole, mebendazole (MBZ) has long been used in human and veterinary medicine to treat parasitic infestations, and is widely employed in the aquaculture of Japanese pufferfish (Takifugu rubripes). However, there have been no studies examining the pharmacokinetic characteristics of MBZ in Japanese pufferfish. Furthermore, the presence of MBZ and its metabolites in animal-derived raw food represents a notable safety concern. Here, we investigated the metabolism of MBZ using a UPLC-Q-TOF system. Additionally, we evaluated the pharmacokinetics of MBZ and two metabolites, 2-amino-5(6)-benzoylbenzimidazole (MBZ-NH₂) and 5-hydroxymebendazole (MBZ-OH), in Japanese pufferfish following intramuscular injection of 20 mg/kg MBZ. We detected three metabolites of MBZ (M1–M3), among which, 2-amino-5(6)-(a-hydroxybenzyl) benzimidazole (M3) was detected in an aquatic animal for the first time. The plasma dispositions of MBZ, MBZ-NH₂, and MBZ-OH were characterized by low plasma clearance, medium distribution volume, and long terminal half-life. Moreover, these compounds were widely distributed in the muscle, from which they were rapidly cleared. The pharmacokinetics and metabolism of mebendazole in Japanese pufferfish are described for the first time in this study. Our findings provide a basis for the rational application of MBZ in Japanese pufferfish farming and contribute to our understanding of the metabolism of MBZ in cultured fish.

摘要

作为典型的广谱苯并咪唑，甲苯咪唑（MBZ）长期以来一直用于人类和兽医治疗寄生虫感染，并广泛用于日本河豚（Takifugu rubripes）的水产养殖。然而，尚无研究检查 MBZ 在日本河豚中的药代动力学特征。此外，动物源性生食中存在 MBZ 及其代谢物是一个值得注意的安全问题。在这里，我们使用 UPLC-Q-TOF 系统研究了 MBZ 的代谢。此外，我们评估了 MBZ 和两种代谢物 2-amino-5(6)-benzoylbenzimidazole (MBZ-NH ₂) 和 5-羟基甲苯达唑 (MBZ-OH)，在日本河豚中肌肉注射 20 mg/kg MBZ 后。我们检测到三种 MBZ 代谢物（M1-M3），其中，2-氨基-5（6）-（a-羟基苄基）苯并咪唑（M3）首次在水生动物中检测到。MBZ、MBZ-NH _{2的等离子体分布}, 和 MBZ-OH 的特点是血浆清除率低, 分布容积中等, 终末半衰期长。此外，这些化合物广泛分布在肌肉中，它们被迅速清除。本研究首次描述了甲苯咪唑在日本河豚体内的药代动力学和代谢。我们的研究结果为MBZ在日本河豚养殖中的合理应用提供了基础，有助于我们了解MBZ在养殖鱼类中的代谢。