Bioavailability of diphenylhydantoin

Abstract

A four‐way crossover study was performed in 8 adult volunteers using a Latin square design with 4 groups of 2 subiects arranged in order of increasing body weight. Single 100 mg doses of diphenylhydantoin (DPH) sodium were administered as an aqueous solution (treatment A), the innovator's capsule (treatment B), alld a commercially available generic capsule (treatment D). A single 300 mg dose (treatment C) was also administered as three 100 mg (innovator's) capsules. DPH capsules from both manufacturers gave plasma levels that were not significantly different at any sampling time. Although DPH follOWing treatment A was absorbed more rapidly, prodUCing higher initial plasma levels than treatments B and D, the areas under the curves for the three treatments were equivalent. The area under the curve for treatment C was also three times that for treatment B. Plasma DPH concentrations were related to the reciprocal of body weight, but plasma protein binding had no effect on the observed intersubiect variance in plasma levels.