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

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  • Peder Carl
  • S Høgskilde
  • T Lang-Jensen
  • V Bach
  • J Jacobsen
  • M B Sørensen
  • M Grälls
  • L Widlund
Vis graf over relationer
Eltanolone, a new intravenous steroid anaesthetic agent was administered intravenously in a dose of 0.6 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 Eltanolone was initially distributed into a relatively large central compartment V1 between 0.09 and 0.98 and then extensively further distributed (Vss between 1.80 and 5.44 and V between 4.87 and 11.87 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)
Bidragets oversatte titelPharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans.
TidsskriftActa Anaesthesiologica Scandinavica
Udgave nummer7
Sider (fra-til)734-741
Antal sider8
StatusUdgivet - 1994

ID: 32511117