Dose dependent suppression of hepatic cytochrome P-450 content by doxorubicin and Mitomycin-C: correlation with antipyrine biotransformation.
Doxorubicin (DOX) and Mitomycin-C (MMC) are two anthraquinones which, when administered to rats, result in a decrease in the content of hepatic cytochrome P-450 and mixed function oxidase activities. DOX administration produced a dose-dependent immediate decrease in cytochrome P-450 content at all doses but a parallel dose-dependent decrease in the rate of antipyrine metabolite formation of the two higher doses. The lower dose of DOX produced an increase in metabolite formation and produced a less than 20% reduction in cytochrome P-450 content. MMC administration produced an immediate, modest (less than 10% of control levels) suppression of hepatic cytochrome P-450 content, and had no effect on antipyrine metabolite formation. These findings demonstrates that two drugs of the same class can produce similar suppressions of cytochrome P-450 content and that a threshold suppression of cytochrome P-450 content is needed to produce alterations in in vivo drug biotransformations.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000378:metabolism*; D001711:Biotransformation; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D065607:Cytochrome P-450 Enzyme Inhibitors; D008937:Mitomycins; D016685:Mitomycin; D004317:Doxorubicin; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase; D000983:Antipyrine