The disposition kinetics of propofol have been determined in 12 patients (six female) receiving propofol 2.5 mg kg-1 for induction of anaesthesia, which was maintained with 67% nitrous oxide in oxygen and 1-1.5% halothane. Peripheral blood samples were collected at selected times up to 8 h after the injection of the drug, and whole blood propofol concentrations determined by HPLC with fluorescence detection. Drug concentration-time data were analysed by the non-linear regression program ELSFIT. This showed the data to be describable by a tri-exponential equation, corresponding to a three-compartment model. There were no differences in the derived kinetic indices for the male and female patients, with the exception of a greater Vdss:V gamma ratio in the males. The terminal half-life in the male patients was 262 min (SEM 44), and in the female patients 309 min (60). Vdss was 329 litre (67) and 313 litre (69) in male and female patients, respectively. The clearance in both groups was 1.8 litre min-1. Seven out of 12 patients showed significant secondary peaks in blood propofol concentration associated with recovery from anaesthesia.

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SummaryIn order to avoid Cremophor-related reactions and reduce the incidence of pain on injection, diisopropylphenol (ICI 35,868; propof) Key wordsAnaesthetics, intravenous; propofol.2,6-di-isopropylphenol (ICI 35,868; propofol; 'Diprivan,' formerly disoprofol) is one of a series of alkylphenols which were found to have anaesthetic properties in animals.' Initial investigations of the pharmacological properties of propofol were conducted using a formulation containing the surfactant Cremophor EL.2 Anaesthetic properties were demonstrated in who received 1-3 mg/kg intravenously although in unpremedicated patients 2 mg/kg was generally successful. s * 7 There was pain on when the drug was given into veins on the dorsum of the hand. To reduce the frequency of this side-effect, and because of circumstantial evidence of a n association of Cremophor-containing agents with anaphylactoid reactions,10-12 an emulsion formulation of propofol has been developed. We have determined the effective dose of propofol* in the new emulsion formulation for induction of anaesthesia in 95% (AD 95) of healthy, unpremedicated patients. MethodsFive hospitals in the United Kingdom participated in an open study for which individual hospital ethics committee approval had been G

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