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.
Dixon
P A
PA
Okereke
S E
SE
Enwelum
M C
MC
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002025:Bufonidae / Q000378:metabolism*; D002415:Cats / Q000378:metabolism; D010856:Columbidae / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D008116:Lizards / Q000378:metabolism*; D008297:Male; D008322:Mammals / Q000378:metabolism*; D008797:Metyrapone / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011284:Pregnenolone / Q000494:pharmacology; D011817:Rabbits / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains / Q000378:metabolism; D012737:Sex Factors; D013045:Species Specificity; D014426:Turtles / Q000378:metabolism*
D000873:Anthracenes; D000431:Ethanol; D011284:Pregnenolone; C034020:anthracene; D010634:Phenobarbital; D008797:Metyrapone