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

Acta Anaesthesiol Scand. 1994 Oct;38(7):734-41. doi: 10.1111/j.1399-6576.1994.tb03987.x.

Abstract

Eltanolone, a new intravenous steroid anaesthetic agent was administered intravenously in a dose of 0.6 mg.kg-1 over 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 t1/2 lambda 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 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-1.kg-1. Eltanolone was initially distributed into a relatively large central compartment V1 between 0.09 and 0.98 l.kg-1 and then extensively further distributed (Vss between 1.80 and 5.44 l.kg-1 and V between 4.87 and 11.87 l.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 with 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anesthetics, Intravenous / adverse effects
  • Anesthetics, Intravenous / pharmacokinetics
  • Anesthetics, Intravenous / pharmacology*
  • Blinking / drug effects
  • Dose-Response Relationship, Drug
  • Half-Life
  • Hemodynamics / drug effects
  • Humans
  • Male
  • Middle Aged
  • Pregnanolone / adverse effects
  • Pregnanolone / pharmacokinetics
  • Pregnanolone / pharmacology*

Substances

  • Anesthetics, Intravenous
  • Pregnanolone