Induction of drug-metabolizing enzymes by the enantiomers of normephenytoin in the rat.
The influence of the S- and R-enantiomers of normephenytoin on various hepatic drug-metabolizing enzyme systems has been investigated in the rat. Both enantiomers proved to be potent enzyme inducers. In vivo, 14C-aminopyrine breath test half-life was decreased and 24-hr urine recovery of 14C after 14C-diphenylhydantoin administration was increased. In vitro, hepatic cytochrome P-450 concentration was increased and there were increases in activity of oxidative metabolism of aminopyrine, aniline, hexobarbital, and p-nitroanisole, and in activities of glucuronyltransferase and glutathionetransferase enzymes. There were differences in the disposition of R- and S-enantiomers indicating that (S)-normephenytoin was eliminated more rapidly. Taking this into consideration, the two enantiomers were equipotent enzyme-inducing agents.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects*; D014453:Glucuronosyltransferase / Q000096:biosynthesis; D006827:Hydantoins / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008617:Mephenytoin / Q000031:analogs & derivatives / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D051381:Rats; D013237:Stereoisomerism
D006827:Hydantoins; C014544:ethylphenylhydantoin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D014453:Glucuronosyltransferase; D008617:Mephenytoin