Combined action of phenobarbital and dexamethasone on the activity of rat liver P450 system.
Phenobarbital and dexamethasone are potent inducers of the same cytochrome P450 form, CYP3A1, but the mechanism of action is not quite clear. If the mechanism of induction by phenobarbital and dexamethasone is different, additive effect may be observed in the specific activities of CYP3A1: ethylmorphine or aminopyrine N-demethylation of liver microsomes from rats treated with phenobarbital and dexamethasone in combination. The results of recent work could not display differences in CYP3A1 activities between the groups of animals single-administered and coadministered with phenobarbital and dexamethasone. However, p-nitrophenol hydroxylation surprisingly increased threefold as a result of double induction. 3-amino-1,2,4-triazole inhibition study shows that CYP2E1 is responsible for 60% of enhanced p-nitrophenol hydroxylase activity, but the residual 40% indicates the participation of other isoenzyme(s).
Monostory
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Central Research Institute for Chemistry, Budapest, Hungary.
Vereczkey
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D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D004790:Enzyme Induction; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A; D010634:Phenobarbital