RT Journal Article
SR Electronic
T1 Stereochemical aspects of the metabolism of 5-ethyl-5-phenylhydantoin (Nirvanol) in the dog.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 393
OP 401
VO 9
IS 5
A1 J H Maguire
A1 B L Kraus
A1 T C Butler
A1 K H Dudley
YR 1981
UL http://dmd.aspetjournals.org/content/9/5/393.abstract
AB Enantiomers of 5-ethyl-5-phenylhydantoin (EPH) were administered to dogs, and urinary metabolites were quantitated. After administration of (R)-EPH, the urinary products included unchanged drug, 5-ethyl-5-(4-hydroxyphenyl)hydantoin (p-EHPH), 5-ethyl-5-(3-hydroxyphenyl)hydantoin (m-EHPH), and an N-glucuronide of EPH. Administration of (S)-EPH gave urinary products consisting of unchanged drug, p-EHPH, m-EHPH, an N-glucuronide of EPH, and a dihydrodiol metabolite, which has been isolated and identified as (5 S)-5-[(3R,4R)-3,4-dihydroxy-1,5-cyclohexadien-1-yl]-5-ethylhydantoin. The levorotatory isomers of p- and m-EHPH have been assigned the (R)-configuration. An unidentified metabolite of EPH has been detected through its reactivity under basic conditions to yield 2-ethyl-2-phenylhydantoic acid, which can be cyclized with acid to EPH. Quantitative studies of the disposition of single oral doses of (R)-, (S)-, and (RS)-EPH by these metabolic routes suggest that the metabolism of one enantiomer is unaffected by the presence of the other enantiomer. Stereoselectivities of metabolic pathways are discussed in relation to stereoselectivities observed for phenytoin metabolism in the dog.