Montesissa C, Anfossi P, Van't Klooster G, Mengelers M
Institute of Veterinary Pathology and Hygiene, Faculty of Veterinary Medicine, University of Padova, Agripolis, Legnaro, Italy.
Vet Res Commun. 1996;20(5):449-60. doi: 10.1007/BF00419182.
The oxidative metabolism of aldicarb (ALD), a carbamate pesticide, and fenbendazole (FBZ), an anthelmintic, was studied using cultured hepatocytes obtained from 4 goats and a bullock and incubated with ALD (50 mumol/L) and FBZ (10 mumol/L). The parent compounds and the metabolites were measured by HPLC. Both compounds are metabolized at the sulphur atom via two sequential oxidations, first to the sulphoxide (aldicarb sulphoxide and oxfendazole, respectively) and then to the sulphone. Oxfendazole and fenbendazole sulphone from FBZ, and aldicarb sulphoxide from ALD were found in both species. Aldicarb sulphone was not produced by the hepatocyte preparations from the bullock. The good correlation obtained comparing the in vitro results of FBZ metabolism with published in vivo data obtained on FBZ kinetics in the same species confirmed the usefulness of in vitro models for predictive analysis of in vivo xenobiotic biotransformations.
使用从4只山羊和1头公牛获取的培养肝细胞,研究了氨基甲酸酯类杀虫剂涕灭威(ALD)和驱虫药芬苯达唑(FBZ)的氧化代谢。将肝细胞与涕灭威(50 μmol/L)和芬苯达唑(10 μmol/L)一起孵育。通过高效液相色谱法测定母体化合物和代谢产物。两种化合物均通过两个连续的氧化反应在硫原子处发生代谢,首先氧化为亚砜(分别为涕灭威亚砜和奥芬达唑),然后再氧化为砜。在两个物种中均发现了来自芬苯达唑的奥芬达唑和芬苯达唑砜,以及来自涕灭威的涕灭威亚砜。公牛的肝细胞制剂未产生涕灭威砜。将芬苯达唑代谢的体外结果与同一物种中已发表的关于芬苯达唑动力学的体内数据进行比较,获得了良好的相关性,这证实了体外模型对于体内外源性生物转化预测分析的有用性。