PHARMACOKINETICS OF THIOPENTAL AND PENTOBARBITAL ENANTIOMERS AFTER INTRAVENOUS ADMINISTRATION OF RACEMIC THIOPENTAL

We studied the pharmacokinetics of thiopental enantiomers in 14 health y 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 bo lus, the total plasma clearance (CL) (295 +/- 132 mL/min) and volume o f distribution at steady state (Vss) (139 +/- 38.5 L) of S-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 volunte ers. The fu of S-thiopental (12.4% +/- 0.6%) was significantly greater than that of S-thiopental (10.0% +/- 1.0%). When the CL and Vss of th e two enantiomers were corrected for the difference in mean fu, there were no significant differences between enantiomers for these variable s. As the 20%-30% difference between the enantiomers in total CL and t otal Vss could be accounted for by stereoselec tivity in fu, these dif ferences are not likely to be clinically significant. During 105-180 m in IV infusion of racemic thiopental to the other patients, there was no difference between enantiomers in mean plasma concentrations of tot al or unbound thiopental or total pentobarbital, a major metabolite of thiopental (P > 0.05). Therefore, it is appropriate to relate pharmac odynamic effects to racemic plasma concentrations of thiopental during IV infusion of racemic thiopental.