METABOLIC FATES OF 3-ETHYL-5-PHENYLHYDANTOIN (ETHOTOIN, PEGANONE), 3-METHYL-5-PHENYLHYDANTOIN AND 5-PHENYLHYDANTOIN

¹ Center for Research in Pharmacology and Toxicology, University of North Carolina School of Medicine, Chapel Hill, North Carolina

Administration of the R,S-forms of 5-phenylhydantoin (I), its 3-methyl derivative (II) or its 3-ethyl derivative (III) to the dog results in excretion of R,S-I in urine. Yields of urinary I indicate that substantial proportions of IIand II undergo N-dealkylation as an initial reaction. Hydroxylation of the phenyl ring in the para-position occurs in II and III. No p-hydroxy derivative of I was found as a metabolite of I, II or III. The p-hydroxy derivatives are present in urine as glucuronides, isolable after release in yields corresponding to less than 1% of the doses of II or III. The R-form of phenyhydantoic acid (XII) was excreted as a major metabolic product of I, II and III. The yields of R(—)-XII from I, II and III were roughly 100, 75 and 60%, respectively, of the R-forms of the administered doses. A conclusion, based on these yields of R(—)-XII and the racemic nature of urinary I, is that the residual S-form of I undergoes racemization in the body.