Pharmacokinetics of thiamylal enantiomers in humans

Int J Clin Pharmacol Ther. 1997 Mar;35(3):128-32.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Blood Proteins / metabolism
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / blood
  • Hypnotics and Sedatives / pharmacokinetics*
  • Hypnotics and Sedatives / therapeutic use
  • Infant
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Protein Binding
  • Seizures / drug therapy
  • Stereoisomerism
  • Thiamylal / administration & dosage
  • Thiamylal / blood
  • Thiamylal / pharmacokinetics*
  • Thiamylal / therapeutic use

Substances

  • Blood Proteins
  • Hypnotics and Sedatives
  • Thiamylal