Stereochemical aspects of the metabolism of 5-ethyl-5-phenylhydantoin (Nirvanol) in the dog.
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.
D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism*; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D004285:Dogs; D005260:Female; D006827:Hydantoins / Q000378:metabolism*; D008617:Mephenytoin / Q000031:analogs & derivatives / Q000378:metabolism*; D009904:Optical Rotation; D009905:Optical Rotatory Dispersion; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D000927:Anticonvulsants; D006827:Hydantoins; C014544:ethylphenylhydantoin; D008617:Mephenytoin