Pharmacokinetics of thiopental and pentobarbital enantiomers after intravenous administration of racemic thiopental

Anesth Analg. 1996 Sep;83(3):552-8. doi: 10.1097/00000539-199609000-00020.

Abstract

We studied the pharmacokinetics of thiopental enantiomers in 14 healthy patients aged 37-73 yr receiving racemic thiopental by intravenous (IV) bolus or IV infusion. Plasma concentration of each enantiomer was measured by chiral high-performance liquid chromatography. After IV bolus, the total plasma clearance (CL) (295 +/- 132 mL/min) and volume of distribution at steady state (Vss) (139 +/- 38.5 L) of R-thiopental were significantly greater than those of S-thiopental (230 +/- 104 mL/min and 114 +/- 47.5 L, respectively). The plasma unbound fraction (fu) was determined by ultrafiltration of plasma from six healthy volunteers. The fu of R-thiopental (12.4% +/- 0.6%) was significantly greater than that of S-thiopental (10.0% +/- 1.0%). When the CL and Vss of the two enantiomers were corrected for the difference in mean fu, there were no significant differences between enantiomers for these variables. As the 20%-30% difference between the enantiomers in total CL and total Vss could be accounted for by stereoselectivity in fu, these differences are not likely to be clinically significant. During 105-180 min IV infusion of racemic thiopental to the other patients, there was no difference between enantiomers in mean plasma concentrations of total or unbound thiopental or total pentobarbital, a major metabolite of thiopental (P > 0.05). Therefore, it is appropriate to relate pharmacodynamic effects to racemic plasma concentrations of thiopental during IV infusion of racemic thiopental.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anesthetics, Intravenous / administration & dosage
  • Anesthetics, Intravenous / pharmacokinetics*
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Hypnotics and Sedatives / pharmacokinetics*
  • Infusions, Intravenous
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Pentobarbital / pharmacokinetics*
  • Stereoisomerism
  • Thiopental / administration & dosage
  • Thiopental / pharmacokinetics*

Substances

  • Anesthetics, Intravenous
  • Hypnotics and Sedatives
  • Pentobarbital
  • Thiopental