INDUCTION OF DRUG-METABOLIZING-ENZYMES BY THE ENANTIOMERS OF NORMEPHENYTOIN IN THE RAT

Google Scholar
  • 1 January 1981
    • journal article
    • research article
    • Vol. 9  (3) , 297-302
Abstract
The influence of the S- and R-enantiomers of normephenytoin on various hepatic drug-metabolizing enzyme systems was investigated in the rat. Both enantiomers were potent enzyme inducers. In vivo, 14C-aminopyrine breath test half-life was decreased and 24 h 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 2 enantiomers were equipotent enzyme-inducing agents.