Metabolic disposition of diphenylhydantoin in normal human subiects following intravenous administration

Abstract

Plasma levels of diphenylhydantoin and the urinary excretion of its hydroxylated metabolite were studied in 6 normal adults following single intravenous doses of 0.25 Gm. DPH‐sodium. The high initial plasma levels dropped rapidly to a mean value of 6.3 µg per milliliter 20 minutes after dosing and 5.2 µg per milliliter in one hour; the plasma half‐life in later time periods was about 15 hours (range 11 to 29 hours). Urinary excretion of free and conjugated HPPH in 5 of the 6 subjects, measured by a new gas‐chromatography procedure, accounted for 76 per cent of the dose (range 65 to 81 per cent) over a period of 5 days. Approximately one third of the administered dose was accounted for by urinary excretion in the first 24 hours, with diminishing amounts being excreted thereafter over periods of 4 to 5 days or more. The maximum excretion rate of HPPH was found to occur about 6 to 8 hours after the intravenous dose, presumably due to an initial delay in the enzymatic processes of hydroxylation or conjugation prior to excretion of the metabolite.