Biopharmaceutical studies on hydantoin derivatives. IV. Factors affecting bioavailability of 5,5-diphenylhydantoin in dog.

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Abstract
Several factors affecting the bioavailability of 5,5-diphenylhydantoin (I) [used for seizure control] and its sodium salt (I-Na) were examined in dogs in relation to meal and the following results were obtained. The bioavailability of I was not appreciably affected by the volume of co-administered water in the range of 30-120 ml. The bioavailability of I was most excellent when I was administered 0.5 h after meal. Food intake 0.5 h after drug administration enhanced appreciably the bioavailability, but that 2 h after drug administration hardly affected the bioavailability. The extent of bioavailability of I-Na was almost 100% of the dose in the range of 100-400 mg/dog when it was administered 0.5 h after meal. When I-Na was administered in the fasting state, the extent of bioavailability was about 60% of the dose. Food-induced enhancement of the bioavailability of I was independent of the food constituents. The bioavailability of I was increased about 1.5-fold and 2-fold with a 10-fold increase in the specific surface area of I in the nonfasting and the fasting states, respectively. Experiments using the dogs with the chronically implanted fistula in the common bile duct showed that the bile was not a major factor contributing to the food-induced enhancement of the bioavailability of I. There was a good correlation between the bioavailability of I in dog and that in man.