Influence of cytochrome P-450 type on the pattern of conjugation of 7-hydroxycoumarin generated from 7-alkoxycoumarins.
Pretreatment of rats with phenobarbitone increased hepatic microsomal 7-methoxy-and 7-ethoxy-coumarin O-dealkylase activities. Pretreatment with beta-naphthoflavone increased only the 7-ethoxycoumarin O-dealkylase activity. The addition of metyrapone in vitro inhibited the O-dealkylations to different extents. Similar results were obtained with diphenyloxazole and ethanol. These results are taken to indicate that different forms of cytochrome P-450 are involved in the O-dealkylation of these two substrates. The pattern of metabolism (Phase I and Phase II) of each alkoxycoumarin in rat isolated hepatocytes was very similar. The sulphate conjugate was the major metabolite produced, the amount of which approached a plateau as the rate of O-dealkylation increased. It is concluded that the type of cytochrome P-450 involved in the initial Phase I metabolism does not influence the subsequent pattern of conjugation.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D003374:Coumarins / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003640:Dealkylation; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity; D014468:Umbelliferones / Q000378:metabolism*; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D003374:Coumarins; D010080:Oxazoles; D014468:Umbelliferones; C017299:7-ethoxycoumarin; D000431:Ethanol; C007929:herniarin; D019324:beta-Naphthoflavone; C031477:7-hydroxycoumarin; D003577:Cytochrome P-450 Enzyme System; C009012:2,5-diphenyloxazole; D010634:Phenobarbital; D008797:Metyrapone