Pharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans

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Abstract
Eltanolone, a new intravenous steroid anaesthetic agent was administered intravenously in a dose of 0.6 mg kg‐1over 45 s to eight healthy male volunteers to evaluate some of its pharmacokinetic and pharmacodynamic effects. Drug concentration–time data were analysed by PCNONLIN, a non–linear regression programme, showing data consistent with a three–compartment model with initial distribution half–life tl/2Xi between 0.3 and 2 min, intermediate distribution half–life 11/22 between 12 and 29 min and terminal half–life tl/2.z between 72 and 212 min. The total body clearance of eltanolone was rapid and with individual values in the range 1.6–2.3 l'h‐1kg‐1. Eltanolone was initially distributed into a relatively large central compartment V| between 0.09 and 0.98 1·kg‐1and then extensively further distributed (Vss between 1.80 and 5.44 1 kg‐1and V between 4.87 and 11.87 1 kg‐1). The excretion of unchanged of eltanolone in urine was very small, the renal clearance was less than 0.5% of the total clearance. Induction of anaesthesia was trouble free with onset and duration of anaesthesia between 1 –2 min and 6–13 min, respectively. There was slight respiratory depression, a small transient increase in heart rate, and a maximum reduction in arterial blood pressure of 23%, as compared widi the resting level. Pain on injection and venous sequelae were not seen. Involuntary movements were seen in one subject. We conclude that eltanolone has a favourable pharmacokinetic profile with relatively rapid half–lives, large distribution volumes and rapid total body clearance. Moreover, eltanolone was found to produce smooth and reliable induction of anaesthesia with only minor cardiorespiratory changes and without pain on injection.