RT Journal Article SR Electronic T1 Absolute configurations of the dihydrodiol metabolites of 5,5-diphenylhydantoin (phenytoin) from rat, dog, and human urine. JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 325 OP 331 VO 8 IS 5 A1 J H Maguire A1 T C Butler A1 K H Dudley YR 1980 UL http://dmd.aspetjournals.org/content/8/5/325.abstract AB Dihydrodiol metabolites (DHD) of phenytoin (PHT) have been extracted from the urine of rats and dogs, and from that of a patient on chronic PHT therapy. The crystalline rat DHD was dehydrated to give a mixture of (S)-5-(4-hydroxyphenyl)-5-phenylhydantoin and (S)-5-(3-hydroxyphenyl)-5-phenylhydantoin. The absolute configuration of C5 of the hydantoin ring of the DHD can accordingly be assigned as (S). Circular dichroism studies allowed further assignment of absolute configuration to the crystalline rat DHD, the metabolite being identified as (5S)-5-[(3R,4R)-3,4-dihydroxy-1,5-cyclohexadien-1-yl]-5-phenylhydantoin, (5S)-DHD. The human DHD metabolite was identical with the (5S)-DHD. The DHD from dog urine was found to be a mixture of diastereoisomers; the major component was identified as (5R)-5-[(3R,4R)-3,4-dihydroxy-1,5-cyclohexadien-1-yl]-5-phenylhydantoin, (5R)-DHD, and the minor diastereoisomer was identified as (5S)-DHD. The ratio (5R)-DHD/(5S)-DHD was approximately 2. A comparison of the absolute configurations of phenolic metabolites of PHT and of the DHD's offered a basis for speculation as to stereochemical aspects of PHT metabolism in the rat, dog, and man.