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

Xenobiotica. 1988 Apr;18(4):429-40. doi: 10.3109/00498258809041679.

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 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.

MeSH terms

  • Adult
  • Emulsions
  • Glucuronates / metabolism
  • Humans
  • Injections, Intravenous
  • Magnetic Resonance Spectroscopy
  • Male
  • Metabolic Clearance Rate
  • Oils
  • Phenols / administration & dosage
  • Phenols / pharmacokinetics*
  • Propofol
  • Time Factors
  • Water

Substances

  • Emulsions
  • Glucuronates
  • Oils
  • Phenols
  • Water
  • Propofol