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  • Title: Pharmacokinetics of thiopental and pentobarbital enantiomers after intravenous administration of racemic thiopental.
    Author: Nguyen KT, Stephens DP, McLeish MJ, Crankshaw DP, Morgan DJ.
    Journal: Anesth Analg; 1996 Sep; 83(3):552-8. PubMed ID: 8780280.
    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.
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