Pharmacokinetics of thiopental and pentobarbital enantiomers after intravenous administration of racemic thiopental.
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.
Nguyen
K T
KT
Victorian College of Pharmacy, Monash University, Melbourne, Victoria, Australia.
Stephens
D P
DP
McLeish
M J
MJ
Crankshaw
D P
DP
Morgan
D J
DJ
D000328:Adult; D000368:Aged; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010424:Pentobarbital / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D013874:Thiopental / Q000008:administration & dosage / Q000493:pharmacokinetics*
D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D010424:Pentobarbital; D013874:Thiopental