Pharmacokinetics of thiopentone enantiomers following intravenous injection or prolonged infusion of rac‐thiopentone

Aims Thiopentone is administered as a racemate (rac‐thiopentone) for induction of anaesthesia as well as for neurological and neurosurgical emergencies. The pharmacokinetics and pharmacodynamics of rac‐thiopentone have been extensively studied but the component R‐(+)‐ and S‐(−)‐ enantiomers, until very recently, have been largely ignored.

Methods The present study analyses the pharmacokinetics of R‐(+)‐ and S‐(−)‐thiopentone in 12 patients given rac‐thiopentone intravenously for induction of anaesthesia and five patients given a prolonged infusion of rac‐thiopentone used for treatment of intracranial hypertension.

Results The mean total body clearance (CL_T ) and apparent volume of distribution at steady‐state (V _ss ) showed trends towards higher values for R‐(+)‐ than for S‐(−)‐thiopentone in both patient groups; CL_T and V_ss of unbound fractions of R‐(+)‐ and S‐(−)‐thiopentone, however, did not show these trends. The time courses of R‐(+)‐ and S‐(−)‐ thiopentone serum concentrations were so similar that EEG effect could not be attributed to one or other enantiomer. Serum protein binding for S‐(−)‐thiopentone was greater than for R‐(+)‐thiopentone (P=0.02) and 24 h urinary excretion of R‐(+)‐thiopentone was greater than for S‐(−)thiopentone (P=0.03). In one patient, concomitant measurement of CSF and serum thiopentone concentrations found that serum: CSF equilibration of unbound fractions of both enantiomers was essentially complete.

Conclusions The study was unable to determine any pharmacokinetic difference of clinical significance between the R‐(+)‐ and S‐(−)‐thiopentone enantiomers and concludes that minor differences in CL_T and V_ss could be explained by enantioselective difference found in serum protein binding.

DOI: 10.1046/j.1365-2125.1997.00567.x

View this article

• Full article (html)
• Enhanced article (html)
• PDF
• References