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1. An intravenous dose of 14C-propofol (0.47 mg/kg) administered to six male volunteers was rapidly eliminated with 88% recovered in the urine in 5 days and less than 2% in faeces. 2. The dose was cleared by metabolism with less than 0.3% excreted unchanged. The major metabolites were the glucuronic acid conjugate of propofol and the glucuronic acid and sulphate conjugates of its hydroxylated derivative, 2,6-diisopropyl-1,4-quinol. Propofol glucuronide accounted for about 53% of the urinary radioactivity and was the major metabolite in plasma from 30 min post dose. 3. The blood concentration of propofol declined in a biphasic manner from a maximum mean value of 0.44 microgram/ml, 2 min after injection. The half-lives of the first and second exponential phases, mean values 5 min and 97 min respectively, varied widely among subjects. A proportion of the dose was cleared slowly, probably due to slow release from less well perfused tissues. Propofol accounted for 94% of the total blood radioactivity at 2 min but only about 6% from 3 to 8 h post dose. 4. Propofol has a volume of distribution equivalent to about 3 to 4 times body weight, and a mean total body clearance of 2.2 1/min.

The pharmacokinetics of propofol (2,6 diisopropylphenol) were compared in 12 patients aged 65-80 yr and 12 patients aged 18-35 yr. After premedication with papaveretum i.m., anaesthesia was induced with propofol 2.0 mg kg-1 in the elderly and 2.5 mg kg-1 in the younger patients. Alcuronium 12-20 mg was then given and the patient's lungs ventilated with halothane and nitrous oxide in oxygen. Blood was taken after various time intervals up to 24 h for the measurement of propofol concentrations by HPLC and for the estimation of propofol protein binding. The mean blood propofol concentration was generally higher in the elderly group, but this difference was only significant at 2 min after induction. The clearance of propofol was significantly lower in the elderly (1.44 +/- 0.10 (SE) litre min-1) than in the younger patients (1.79 +/- 0.12 litre min-1). The volume of the central compartment in the elderly patients was significantly smaller (19.6 +/- 5.2 litre) than that in the young (26.3 +/- 2.9 litre). There was no difference in the volume of distribution at equilibrium (1608 +/- 246 litre in the elderly and 1757 +/- 360 litre in the young), in the volume of distribution at steady state (691 +/- 139 litre in the elderly and 771 +/- 236 litre in the young) or in the half-lives of distribution and elimination. The plasma protein binding of propofol was similar in both groups and showed no trend with time after dose.

1. The pharmacokinetics of propofol in an emulsion formulation ('Diprivan') have been studied after single bolus doses to rats, dogs, rabbits and pigs, and after single and multiple infusions to dogs. Venous blood propofol concentrations were determined by h.p.l.c. with u.v. or fluorescence detection. Curve fitting was performed using ELSFIT. 2. The distribution of propofol in blood and its plasma protein binding have been studied in rat, dog, rabbit and man. Protein binding was high (96-98%), and in most species propofol showed appreciable association with the formed elements of blood. 3. Where an adequate sampling period was employed the pharmacokinetics of propofol were best described by a three-compartment open 'mammillary' model. Propofol was distributed into a large initial volume (1-21/kg) and extensively redistributed (Vss = 2-10 x body weight) in all species. Clearance of propofol by all species was rapid, ranging from about 30-80 ml/kg per min in rats, dogs and pigs to about 340 ml/kg per min in rabbits.

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