Sulfoxidation of albendazole by a cytochrome P450-independent monooxygenase from rat liver microsomes
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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 μM 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).
KeywordsSulfoxide Phenobarbital Liver Microsome Flavin Albendazole
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