A. Wessen et al., CONCENTRATION-EFFECT RELATIONSHIPS OF ELTANOLONE GIVEN AS A BOLUS DOSE OR CONSTANT RATE INTRAVENOUS-INFUSION TO HEALTHY MALE-VOLUNTEERS, Anesthesiology, 84(6), 1996, pp. 1317-1326
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.