[Diazepam metabolism by multiple forms of cytochrome P-450 in rat liver microsomes].
The synthesis of pharmacologically active diazepam metabolites (oxazepam, 4-hydroxydiazepam, N-demethyldiazepam) in liver microsomes of intact and phenobarbital-, 3-methylcholanthrene- and dexamethasone-induced male and female Wistar rats as well as in a reconstituted system with isolated forms of cytochrome P-450 (P-450a, P-450b, P-450c, P-450d and P-450k according to the Ryan nomenclature) was studied. Marked sex-dependent differences in the rates of diazepam metabolism in liver microsomes of intact and induced animals were revealed. The changes in the spectrum of diazepam metabolites in liver microsomes of induced rats (as compared to control animals) were revealed. In a reconstituted system only phenobarbital-induced cytochromes P-450b and P-450k were found to be active participants of diazepam N-demethylation; none of the isoenzymes tested were shown to be involved in diazepam hydroxylation.
Faĭbushevich
A A
AA
Guliaeva
L F
LF
Grishanova
A Iu
AIu
Mishin
V M
VM
Liakhovich
V V
VV
D000818:Animals; D001711:Biotransformation; D003580:Cytochromes / Q000096:biosynthesis / Q000378:metabolism*; D003640:Dealkylation; D003907:Dexamethasone / Q000494:pharmacology; D003975:Diazepam / Q000378:metabolism* / Q000493:pharmacokinetics; D004790:Enzyme Induction; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism*; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D003580:Cytochromes; D007527:Isoenzymes; D008748:Methylcholanthrene; D003907:Dexamethasone; D003975:Diazepam; D010634:Phenobarbital
Metabolizm diazepama mnozhestvennymi formami tsitokhroma P-450 mikrosom pecheni krys.