Diphenylhydantoin Metabolism in Uremia

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Abstract
Diphenylhydantoin was administered orally or intravenously to 20 uremic and 20 nonuremic patients. In the former this drug and 5-phenyl-5-parahydroxyl-phenylhydantoin, its major metabolite, were measured in blood and urine. In the nonuremic patients, only diphenylhydantoin levels in plasma were measured. Regardless of the route of administration, diphenylhydantoin concentrations were uniformly lower in uremic than in nonuremic patients. In uremic patients, plasma concentrations of 5-phenyl-5-parahydroxyl-phenylhydantoin were higher than reported values in nonuremic subjects. After a single intravenous injection of 250 mg of diphenylhydantoin, its rate of elimination from plasma (half-life) was 8.1 hours in five uremic patients and 13.0 hours in three nonuremic subjects. These observations suggest an altered metabolic disposition of the drug in uremia.