THE SYSTEMIC AND CEREBRAL KINETICS OF THIOPENTAL IN SHEEP - ENANTIOMERIC ANALYSIS

Thiopental is used as a racemate (rac-thiopental). Enantiomeric pharma cokinetic differences could therefore influence the onset and duration of anesthesia of rac-thiopental. We studied the systemic and cerebral kinetics of R(+)- and S(-)-thiopental in five adult ewes after a 2-mi n intravenous infusion of 500 mg rac-thiopental sodium. Systemic kinet ic values were determined from the time course of concentrations in ar terial plasma; cerebral kinetic values were deduced from the time cour se of the concentration differences between arterial and superior sagi ttal sinus blood plasma. Enantiomeric differences were found in both s ites, with the (R:S) ratio of thiopental enantiomer blood concentratio ns initially being greater than or equal to 1 then decreasing to <1 af ter approximately 60 min. This is consistent with the finding of the m ean total body clearance of R(+)-thiopental being 17% (SD 12%) greater than that of S(-)-thiopental (P = .04). Sagittal sinus plasma concent rations of both enantiomers followed closely behind those in arterial plasma and this is consistent with facile bidirectional exchange of th iopental between plasma and brain. No significant differences were fou nd between enantiomers in the rates of brain influx or efflux. Onset a nd regression of anesthesia occurred while the enantiomer blood concen trations were similar. Hence published pharmacokinetic-pharmacodynamic models of the onset of thiopental effects probably are not significan tly compromised by neglecting the enantiomeric duality of thiopental, but models based on its elimination kinetics could be compromised if e nantiomeric differences are neglected.