PHARMACOKINETICS AND PHARMACODYNAMICS OF ELTANOLONE (PREGNANOLONE), ANEW STEROID INTRAVENOUS ANESTHETIC, IN HUMANS

Eltanolone, a new intravenous steroid anaesthetic agent was administer ed intravenously in a dose of 0.6 mg . kg(-1) over 45 s to eight healt hy male volunteers to evaluate some of its pharmacokinetic and pharmac odynamic effects. Drug concentration-time data were analysed by PCNONL IN, a non-linear regression programme, showing data consistent with a three-compartment model with initial distribution half-life t1/2 lambd a(1), between 0.3 and 2 min, intermediate distribution half-life t1/2 lambda(2) between 12 and 29 min and terminal half-life t1/2 lambda(2), behveen 72 and 212 min. The total body clearance of eltanolone was ra pid and with individual Values in the range 1.6-2.3 1 . h(-1) . kg(-1) . Eltanolone was initially distributed into a relatively large central compartment V-1 between 0.09 and 0.98 1 . kg(-1) and then extensively further distributed (Vss between 1.80 and 5.44 1 . kg(-1) and V betwe en 4.87 and 11.87 1 . kg(-1)). The excretion of unchanged of eltanolon e in urine was very small; the renal clearance was less than 0.5% of t he total clearance. Induction of anaesthesia was trouble free with ons et and duration of anaesthesia between 1-2 min and 6-13 min, respectiv ely There was slight respiratory depression, a small transient increas e in heart rate, and a maximum reduction in arterial blood pressure of 23%, as compared with the resting level. Pain on injection and venous sequelae were not seen. Involuntary movements were seen in one subjec t We conclude that eltanolone has a favourable pharmacokinetic profile with relatively rapid half-lives, large distribution volumes and rapi d total body clearance. Moreover, eltanolone was found to produce smoo th and reliable induction of anaesthesia with only minor cardiorespira tory changes and without pain on injection.