Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of 14C-propofol.
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.
Simons
P J
PJ
Safety of Medicines Department, Imperial Chemical Industries PLC, Macclesfield, Cheshire, UK.
Cockshott
I D
ID
Douglas
E J
EJ
Gordon
E A
EA
Hopkins
K
K
Rowland
M
M
D000328:Adult; D004655:Emulsions; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008657:Metabolic Clearance Rate; D009821:Oils; D010636:Phenols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015742:Propofol; D013997:Time Factors; D014867:Water
D004655:Emulsions; D005965:Glucuronates; D009821:Oils; D010636:Phenols; D014867:Water; D015742:Propofol