CONCENTRATION-EFFECT RELATIONSHIPS OF ELTANOLONE GIVEN AS A BOLUS DOSE OR CONSTANT RATE INTRAVENOUS-INFUSION TO HEALTHY MALE-VOLUNTEERS

Background: The primary purpose of this study was to evaluate concentr ation-effect relationships of the new steroid anesthetic eltanolone du ring recovery from a bolus dose and constant rate intravenous infusion in healthy male volunteers. Methods: Ten subjects received a bolus do se of 0.75 mg/kg eltanolone over 20 s. A 2-h constant rate intravenous infusion of eltanolone was given to five subjects at a rate of 2 mg . kg(-1). h(-1) and to another five subjects at a rate of 3.5 mg . kg(- 1). h(-1). Recovery performance was assessed as the time required to r each different end-points and by means of three different psychomotor tests. Results: A low interindividual variability was found in the ser um concentration of eltanolone at the pharmacodynamic end-points durin g recovery. The Cp(50) value for ''eye opening'' was 382 mu g/1 (95% c onfidence interval, 285-489) after a bolus dose corresponding to a med ian time of 16 min (range 8-25), After eltanolone infusion, the Cp(50) value for ''eye opening'' was 507 mu g/1 (95% confidence interval, 42 5-605) and the corresponding median time was 21 min (range 8-25) in th e low-dose group and 49 min (range 31-66) in the high-dose group, The Cp(50) values at the same effect end-points in the bolus group were le ss than those in the infusion groups, probably because of insufficient equilibration time between serum and the effect compartment. Conclusi ons: Recovery characteristics of eltanolone were predictable because o f a relatively low interindividual variability in serum concentrations but with a slow blood:effect compartment equilibration.