Enantioselective pharmacokinetics of ethotoin in humans following single oral doses of the racemate

✍ Scribed by Dr. Wayne D. Hooper; Nerida J. O'shea; Mi Sui Qing

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 655 KB
• Volume: 4
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/chir.530040303

✦ Synopsis

Racemic ethotoin (lo00 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 enantioselectively 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 G,, and AUCG, values for (+)-(S)-ethotoin were significantly greater than those for (-)-(R)-ethotoin (ratio of mean AUCG, values 0.88), but the elimination half-lives of the isomers were virtually identical [12.35 f 5.15 h for ( -)-(R)-ethotoin; 12.28 f 5.34 h for ( + )-(3-ethotoin]. Parameters derived from AUC&_, (Cb /F and V,, /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 f 6.11 h) than that of ethotoin. Enantioselectivity in the pharmacokinetics of ethotoin is therefore a minor issue.