title: Studies of the metabolism of 5,5-diphenylhydantoin relating principally to the stereoselectivity of the hydroxylation reactions in man and the dog.
abstract: The hydroxylated metabolites of 5,5-diphenylhydantoin (DPH) in dog and human urine, after release by beta-glucuronidase, have been isolated and purified by procedures entailing only solvent partitioning without crystallization or any other procedure that could change the proportions of optical isomers. Dogs produced both the meta- and para-5-hydroxyphenyl-5-phenylhydantoins (m-HPPH and p-HPPH) from DPH, the former in approximately 6 times the amount of the latter. The m-HPPH from dog urine was dextrorotatory and had the properties of a pure optical isomer. The p-HPPH from dog urine was a mixture of optical isomers with approximately a 2:1 preponderance of the levorotatory isomer. When dog urine was heated with acid rather than treated with beta-glucuronidase, the isolated p-HPPH contained a small preponderance of the dextrorotatory isomer, probably owing to production of d-p-HPPH from the dihydrodiol metabolite. No o-HPPH was found in dog urine. When racemic p-HPPH and m-HPPH were administered to dogs, there was little if any preponderance of either optical isomer in the materials isolated from urine. Enzymatically released p-HPPH isolated from urine of human patients receiving DPH was a mixture of optical isomers with approximarely a 10:1 preponderance of the levorotatory isomer. Crystallization of this material readily yields pure l-p-HPPH. Human urine contained only very small amounts of m-HPPH, which was detectable by gas chromatography but insufficient in amount to permit isolation. Hypotheses are discussed that could account for the differences in the metabolism of DPH in man and dog. Small amounts of 2,2-diphenylhydantoic acid were found in urine of dogs but not of human patients receiving DPH.
mesh_terms: D000818:Animals; D004285:Dogs; D005260:Female; D005966:Glucuronidase; D006801:Humans; D006900:Hydroxylation; D007536:Isomerism; D010672:Phenytoin / Q000378:metabolism* / Q000652:urine; D012995:Solubility; D013237:Stereoisomerism
chemical_list: D010672:Phenytoin; D005966:Glucuronidase