Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of ¹⁴C-propofol

Abstract

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 μg/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.