Pharmacokinetics of thiamylal enantiomers in humans
Sueyasu, M.; Ikeda, T.; Taniyama, T.; Futugami, K.; Kataoka, Y.; Oishi, R.
International Journal of Clinical Pharmacology and Therapeutics 35(3): 128-132
1997
ISSN/ISBN: 0946-1965 PMID: 9089003 Document Number: 481895
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 lt 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 l/hr/kg) was 1.8 times greater (p lt 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 lt 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.