Concentration-effect relationships of eltanolone given as a bolus dose or constant rate intravenous infusion to healthy male volunteers.
ABSTRACT The primary purpose of this study was to evaluate concentration-effect relationships of the new steroid anesthetic eltanolone during recovery from a bolus dose and constant rate intravenous infusion in healthy male volunteers.
Ten subjects received a bolus dose 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 reach different end-points and by means of three different psychomotor tests.
A low interindividual variability was found in the serum concentration of eltanolone at the pharmacodynamic end-points during recovery. The Cp50 value for "eye opening" was 382 micrograms/L (95% confidence interval, 285-489) after a bolus dose corresponding to a median time of 16 min (range 8-25). After eltanolone infusion, the Cp50 value for "eye opening" was 507 micrograms/L (95% confidence interval, 425-605) and the corresponding median time was 21 min (range 8-25) in the low-dose group and 49 min (range 31-66) in the high-dose group. The Cp50 values at the same effect end-points in the bolus group were less than those in the infusion groups, probably because of insufficient equilibration time between serum and the effect compartment.
Recovery characteristics of eltanolone were predictable because of a relatively low interindividual variability in serum concentrations but with a slow blood:effect compartment equilibration.
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ABSTRACT: Ten male volunteers received a 1-min i.v. infusion of a new water soluble steroid anaesthetic agent, ORG 21465. Individuals received doses ranging from 0.8 to 1.8 mg kg-1. All subjects experienced venous pain at the site of injection; those receiving 1.0 mg kg-1 or more became anaesthetized. There was no evidence of histamine release and apnoea did not occur. Excitatory phenomena were observed in all subjects and were dose related; no spikes were seen on the EEG. Pharmacokinetic analysis supported a three-compartment (non-weight-related) model with compartmental volumes V1, V2 and V3 of 4.31, 14.2 and 89.4 litre, respectively. Clearance from the central compartment V1 was 1.55 litre min-1. Inter-compartmental clearances Q1 and Q2 were 2.54 and 1.79 litre min-1. We found that ORG 21465 was an effective anaesthetic in humans. The relationship between sedation, anaesthesia and excitation requires further exploration.BJA British Journal of Anaesthesia 11/1997; 79(4):427-32. · 4.24 Impact Factor