Sulfoxidation of albendazole by a cytochrome P450-independent monooxygenase from rat liver microsomes.
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).
D015766:Albendazole / Q000031:analogs & derivatives*; D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010105:Oxygenases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D015766:Albendazole; C027186:albendazole sulfoxide