Conversion of Phenytoin to Reactive Metabolites in Rat Liver Microsomes
The widely used anticonvulsant drug phenytoin (PHT) is primarily metabolized by aromatic hydroxylation. It is presumed that liver microsomal cytochrome(s) P450 catalyze the formation of an epoxide intermediate which gives rise to the major metabolite, 5-(4-hydroxyphenyl)-5- phenylhydantoin (4-HPPH)1,2 and a 3,4-dihydrodiol metabolite (DHD).3 In addition, PHT is converted to a catechol metabolite [5-(3,4-dihydroxyphenyl)-5-phenylhydantoin,CAT].4–7 CAT is formed from both 4-HPPH and DHD, although the predominate route is via 4-HPPH.8
KeywordsXanthine Oxidase High Pressure Liquid Chromatography Covalent Binding Reactive Metabolite Cyclohexene Oxide
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