Fargetton X, Galtier P, Delatour P
Vet Res Commun. 1986 Jul;10(4):317-24. doi: 10.1007/BF02213995.
The in vitro biological oxidation of albendazole to albendazole sulfoxide by rat liver microsomes has been studied. This reaction corresponds to a NADPH-dependent enzymatic system, characterised by Km and Vm values of 53.6 microM and 0.59 nmole/mg protein per min. The rate of sulfoxidation by liver microsomes of rats treated with phenobarbital, B-naphthoflavone, Aroclor 1254 and 3-methylcholanthrene was not increased. SKF 525A and metyrapone did not inhibit albendazole sulfoxidase. Thiobenzamide and tranylcypromine decreased sulfoxidation to 48 and 52% of control values. The inhibition by tranylcypromine was competitive. Purified flavin adenine dinucleotide (FAD)-containing monooxygenase from hog liver microsomes catalysed sulfoxidation of albendazole (V = 0.52 nmole/nmole enzyme per min). The present data demonstrate that sulfoxidation of albendazole in the rat liver is not catalysed by a cytochrome P450-dependent monooxygenase and suggest that albendazole is a substrate for FAD-containing monooxygenase (FMO).
已对大鼠肝微粒体将阿苯达唑体外生物氧化为阿苯达唑亚砜进行了研究。该反应对应于一种依赖NADPH的酶系统，其特征在于Km和Vm值分别为53.6微摩尔和每分钟0.59纳摩尔/毫克蛋白质。用苯巴比妥、β-萘黄酮、多氯联苯混合物1254和3-甲基胆蒽处理的大鼠肝微粒体的亚砜氧化速率没有增加。SKF 525A和甲吡酮不抑制阿苯达唑亚砜氧化酶。硫代苯甲酰胺和反苯环丙胺将亚砜氧化降低至对照值的48%和52%。反苯环丙胺的抑制作用具有竞争性。从猪肝微粒体中纯化的含黄素腺嘌呤二核苷酸（FAD）的单加氧酶催化阿苯达唑的亚砜氧化（V =每分钟0.52纳摩尔/纳摩尔酶）。目前的数据表明，大鼠肝脏中阿苯达唑的亚砜氧化不是由细胞色素P450依赖性单加氧酶催化的，并表明阿苯达唑是含FAD单加氧酶（FMO）的底物。
