Phenytoin metabolism in the cat after long-term oral administration

The metabolism of sodium phenytoin (PHT) in the cat was studied by gas-liquid chromatographic analyses of the drug and its metabolites extracted from plasma, urine, and feces during a 5-month course of daily oral administration. Plasma PHT levels of 15-18 micrograms/ml were observed. Urine contained 5-(4-hydroxyphenyl)-5-phenylhydantoin, 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)-5-phenylhydantoin, 1-deoxy-1-(5,5-diphenylhydantoin-3-yl)-beta-D-glucopyranuronate, and unmetabolized PHT. Large quantities of PHT (32-63% of the daily dose) were observed in feces. We suggest that gastrointestinal malabsorption, extensive N-glucuronidation, and limited hydroxylation determine the fate of orally administered PHT in the cat. This is not the case in humans.