Influence of species, sex and drug pretreatment on the metabolism of metyrapone

The metabolism of metyrapone was investigated in three mammalian and four non-mammalian species, and keto reduction was found to be the major metabolic route (except in the cat). Toad, lizard and tortoise did not form metyrapone N-oxides. Rat and cat formed both isomeric N-oxides of metyrapone, whereas rabbit and pigeon have a limited capacity to form only the N-oxide II and N-oxide I, respectively. There were marked sex differences in both keto reduction and N-oxidation in the rat. Anthracene did not affect metyrapone N-oxides formation in the male rat; however phenobarbitone and pregnenolone significantly induced N-oxide II formation, whereas ethanol induced both isomeric N-oxides formation. Cimetidine, a known cytochrome P-450 inhibitor, inhibited the N-oxide II formation but with an enhanced N-oxide I formation.