Pregnanolone emulsion A preliminary pharmacokinetic and pharmacodynamic study of a new intravenous anaesthetic agent

Abstract

Pregnanolone emulsion, a new steroid anaesthetic agent, was administered intravenously as bolus doses to six young healthy male volunteers in a preliminary pharmacokinetic and pharmacodynamic study. The plasma concentration-time curves fitted a two-compartment model. The elimination half-life was between 0.9 and 1.4 hours, volume of central compartment between 0.95 and 2.10 litres/kg, volume of distribution between 3.75 and 5.58 litres/kg and total body clearance between 1.80 and 3.07 (litres/hour)/kg. The excretion in urine of unchanged pregnanolone was less than 0.1%. The pharmacodynamic properties were found to be similar to those of Althesin, with immediate induction of anaesthesia of short duration. The anaesthetic affected haemodynamics only slightly; minor depression of ventilation, with an increase in PaCO2, occurred in several of the subjects. Excitation of short duration occurred in one subject during induction of sleep and slight involuntary muscle movements in another subject during sleep. It is impossible to draw any clear conclusions of the clinical efficacy and tolerance from this limited normal subject trial, but pregnanolone emulsion seems worthy of further clinical trial.