Enantioselective pharmacokinetics of ethotoin in humans following single oral doses of the racemate.
Racemic ethotoin (1000 mg) was administered orally as a single dose to six healthy adult volunteers. Blood samples were collected at appropriate times for 120 h following the dose. Ethotoin was quantified enantio-selectively in plasma using a novel chiral column HPLC procedure. One of the enantiomers of the chiral metabolite, 5-phenylhydantoin, was also quantified in the HPLC method. The Cmax and AUC0-infinity values for (+)-(S)-ethotoin were significantly greater than those for (-)-(R)-ethotoin (ratio of mean AUC0-infinity values 0.88), but the elimination half-lives of the isomers were virtually identical [12.35 +/- 5.15 h for (-)-(R)-ethotoin; 12.28 +/- 5.34 h for (+)-(S)-ethotoin]. Parameters derived from AUC0-infinity (Cl0/F and V(area)/F) also differed slightly between the isomers. The data were interpreted as indicating a small difference in the absorption of the two isomers; it seemed unlikely, in terms of the identical elimination rates, that their metabolic profiles would differ greatly. The 5-phenylhydantoin was eliminated with a significantly longer half-life (18.69 +/- 6.11 h) than that of ethotoin. Enantioselectivity in the pharmacokinetics of ethotoin is therefore a minor issue.
Department of Medicine, University of Queensland, Australia.
W D
WD
Hooper
N J
NJ
O'Shea
M S
MS
Qing
D000284:Administration, Oral; D000328:Adult; D005260:Female; D006801:Humans; D006827:Hydantoins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D013237:Stereoisomerism
D006827:Hydantoins