1. The steroid antagonist RU38486 is metabolized by the liver microsomal P450 mono-oxygenases.
- Author
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Chasserot-Golaz S, Ribeiro V, Genot G, Lechner MC, and Beck G
- Subjects
- Aging, Animals, Antibodies, Biotransformation, Cytochrome P-450 Enzyme System immunology, Kinetics, Male, Methylcholanthrene pharmacology, Microsomes, Liver drug effects, Phenobarbital pharmacology, Rats, Rats, Inbred Strains, Reference Values, Cytochrome P-450 Enzyme System metabolism, Liver growth & development, Microsomes, Liver enzymology, Mifepristone metabolism
- Abstract
Microsomal preparations from adult male rat liver actively oxidized RU38486 into the 11 beta-monodemethylated, 11 beta-didemethylated and 17 alpha-hydroxylated derivatives, metabolites which are known to be formed in vivo. These oxidative reactions were inhibited at different degrees by P450 chemical inhibitors. Pretreatment of the animals by P450 mono-oxygenase prototype inducers led to drastic changes in RU38486 metabolization. Methylcholanthrene treatment carried out a significant decrease while phenobarbital markedly increased the metabolic activity of the liver microsomes. Moreover, antibodies to methylcholantrene-inducible P450 forms did not affect the metabolic activity while a complete blockade-of RU38486 oxidation was observed in the presence of antibodies to phenobarbital- inducible forms. The present results demonstrate that liver P450 mono-oxygenases are engaged in different oxidative steps of RU38486 metabolism and that phenobarbital-inducible but not methylcholanthrene-inducible P450 forms are active in RU38486 degradation.
- Published
- 1990
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