Biotransformation of azapetine to oxazapetine in rat and rabbit liver fractions.

The biotransformation of azapetine (I) to a lactam metabolite, oxazapetine (II), has been investigated in rat and rabbit hepatic subcellular fractions. In the presence of NADPH, II was produced from I in incubation mixtures containing 9000 g supernatant fraction or combined microsomes and cytosol, but not in mixtures containing microsomes or cytosol alone. Production of II was also observed when dehydrozapetine (III) was incubated with rabbit 9000 g supernatant fraction or cytosol. In washed rabbit microsomes II was not produced from III, but I was converted to III in the presence of NADPH. These results suggested that the biotransformation is initiated by microsomal enzymatic oxidation of I to III, followed by further oxidation of III to II by a soluble enzyme.