Kinetic and spectral studies of type i and type Ii compounds with rat hepatic microsomes in the presence of the major metabolite of diphenylhydantoin
Stavchansky, S.A.; Kostenbauder, H.B.; Lubawy, W.C.
Drug Metabolism and Disposition the Biological Fate of Chemicals 3(6): 557-564
1975
ISSN/ISBN: 0090-9556 PMID: 1233 Document Number: 86557
The nature of the inhibitory effects of the major metabolite of diphenylhydantoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), on the in vitro metabolism of ethylmorphine and aniline by rat hepatic microsomes was examined. The N-demethylation of ethylmorphine was competitively inhibited by HPPH, whereas inhibition of the hydroxylation of aniline was not competitive. The spectrum produced by HPPH when added to microsomal suspensions does not resemble the classical type I or type II spectra, but rather a reversed type I spectrum. Spectral evidence is presented indicating that HPPH also diminishes the magnitude of the spectral change produced by type I and II compounds.