title: Pharmacokinetics of thiamylal enantiomers in humans.
abstract: Thiamylal, a chiral thiobarbiturate, is marketed as the racemate. The pharmacokinetic behavior of thiamylal enantiomers was studied in patients undergoing thiamylal treatment. The percentage of R(+)-thiamylal unbound to serum protein was 1.5 times greater than that of S(-)-enantiomer (17.5 +/- 2.6% and 11.7 +/- 2.0% mean +/- SD, p < 0.001, n = 7). The pharmacokinetic parameters of enantiomers were estimated in 6 patients. S(-)-thiamylal serum concentration was higher than R(+)-enantiomer in all patients at all time points examined. Total clearance of R(+)-thiamylal (0.27 +/- 0.23 1/hr/kg) was 1.8 times greater (p < 0.05) than that of S(-)-thiamylal (0.15 +/- 0.13). The volume of distribution at steady state of R(+)-thiamylal (3.66 +/- 1.99 l/kg) was 1.4 times higher (p < 0.05) than that of S(-)-enantiomer (2.60 +/- 1.35). The differences in these parameters may be due mainly to enantioselective binding to serum protein.
authors.affiliation: Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sueyasu
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
authors.forename: T
authors.initials: T
authors.lastname: Taniyama
authors.forename: K
authors.initials: K
authors.lastname: Futugami
authors.forename: Y
authors.initials: Y
authors.lastname: Kataoka
authors.forename: R
authors.initials: R
authors.lastname: Oishi
mesh_terms: D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D012640:Seizures / Q000188:drug therapy; D013237:Stereoisomerism; D013840:Thiamylal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D001798:Blood Proteins; D006993:Hypnotics and Sedatives; D013840:Thiamylal