The fate of orally administered [4-l4C]phenytoin in two healthy male volunteers

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Abstract
Whether phenytoin (DPH), like the barbiturates, is metabolized via the recently discovered N-glucosidation pathway was studied. Virtually 100% of the ingested 14C-labeled doses in 2 subjects could be accounted for in the excreta within 5 days, with 35% in feces and 65% in urine. Radioactivity in the urine was entirely due to free and conjugated 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) and the dihydrodiol, and that in the feces mostly due to the unmetabolized drug. There was no indication of phenytoin N-glucoside being excreted in either the urine or feces of either subject, although one of the subjects possessed a particularly strong N-glucosidation capacity for barbiturates. The other subject was a poor metabolizer of debrisoquine and sparteine. The DPH disappearance from serum and the DPH metabolite excretion in urine were virtually alike in these 2 subjects, indicating that the debrisoquine 4-hydroxylating and DPH hydroxylating capacities may be separable entities.

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