Biopharmaceutical studies on hydantoin derivatives. II. Pharmacokinetics and bioavailability of hydantoin derivatives in dogs.

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Abstract
Pharmacokinetics and bioavailability for the 1-benzenesulfonylhydantoin derivatives and 1-unsubstituted hydantoin derivatives [anticonvulsants] were evaluated from the plasma concentrations after oral and i.v. administrations to dogs. Apparent volume of distribution of the 1-benzenesulfonylhydantoin derivatives was .apprx. 0.25 l/kg, while that of the 1-unsubstituted hydantoin derivatives was .apprx. 1.3 l/kg. Apparently, introduction of the benzenesulfonyl group at the 1-position of the hydantoin ring has marked effect on the distribution into the fluids and tissues of the body. Bioavailabilities of sodium 5,5-diphenylhydantoin and sodium 1-benzenesulfonyl-5,5-diphenylhydantoin exceeded those of their corresponding free forms. The results were well explicable in terms of the excellent dissolution behaviors of the salt forms. The bioavailabilities of 5-ethyl-5-phenylhydantoin and 1-benzenesulfonyl-5-ethyl-5-phenylhydantoin were almost perfect. Apparently, the dissolution rate is a rate-determining step in the bioavailability of the derivatives having 2 phenyl groups at 5-position of the hydantoin ring, irrespective of the presence of the benzenesulfonyl group at the 1-position.

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