PHARMACOKINETICS OF THIOPENTONE ENANTIOMERS FOLLOWING INTRAVENOUS-INJECTION OR PROLONGED INFUSION OF RAC-THIOPENTONE

Aims Thiopentone is administered as a racemate (rac-thiopentone) for i nduction of anaesthesia as well as for neurological and neurosurgical emergencies. The pharmacokinetics and pharmacodynamics of vac-thiopent one have been extensively studied but the component R-(+)- and S-(-)- enantiomers, until very recently, have been largely ignored. Methods T he present study analyses the pharmacokinetics of R-(+)- and S-(-)-thi opentone in 12 patients given rac-thiopentone intravenously for induct ion of anaesthesia and five patients given a prolonged infusion of vdc -thiopentone used for treatment of intracranial hypertension. Results The mean total body clearance (CLT) and apparent volume of distributio n at steady-state (V-ss) showed trends towards higher values for R-(+) - than for S-(-)-thiopentone in both patient groups; CLT and V-ss of u nbound fractions of R-(+)- and S-(-)-thiopentone, however, did not sho w these trends. The time courses of R-(+)- and S-(-)- thiopentone seru m concentrations were so similar that EEG effect could not be attribut ed to one or other enantiomer. Serum protein binding for S-(-)-thiopen tone 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 thi opentone concentrations found that serum: CSF equilibration of unbound fractions of both enantiomers was essentially complete. Conclusions T he study was unable to determine any pharmacokinetic difference of cli nical significance between the R-(+)- and S-(-)-thiopentone enantiomer s and concludes that minor differences in CLT and V-ss could be explai ned by enantioselective difference found in serum protein binding.