Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of¹⁴C-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 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.

Death after excessive propofol abuse

“…Propofol was mainly metabolized by two pathways: either direct glucuronide conjugation or p-hydroxylation with subsequent glucuronidation (or sulphation) [11]. Only very small amounts were eliminated without metabolization [10,11]. Acidic urine hydrolysis increased the propofol concentration from 5.4µg/ml to 8900µg/ml.…”

“…Analytical results of propofol determination in blood, urine, and various organs are summarised in Table 1. Propofol was mainly metabolized by two pathways: either direct glucuronide conjugation or p-hydroxylation with subsequent glucuronidation (or sulphation) [11]. Only very small amounts were eliminated without metabolization [10,11].…”

“…Propofol is maily metabolised by two pathways: either direct glucronide conjugation or p-hydroxylation with subsequent glucuronidation (or sulphation) [11] where quinol glucuronide amounts to 20-50% of the dose [12]. Only very small amounts are aliminated without being metabolised [10,11]. We report on the death of a male nurse found dead in his flat with several empty propofol ampoules littering the floor.…”

“…The last half-life corresponds to the elimination from adipose tissue [10], but being insignificant due to the rapid metabolism of propofol. Propofol is maily metabolised by two pathways: either direct glucronide conjugation or p-hydroxylation with subsequent glucuronidation (or sulphation) [11] where quinol glucuronide amounts to 20-50% of the dose [12]. Only very small amounts are aliminated without being metabolised [10,11].…”

Therapeutic concentrations of propofol protects mouse macrophages from nitric oxide-induced cell death and apoptosis

“…1 Metabolism of PPF by cytochrome P450-dependent monooxygenases to 2,6-diisopropyl-1,4-quinol or uridine diphosphate glucuronosyltransfease-mediated glucuronidation to glucuronide complex may be another reason explaining the decreasing protective effect of the iv anesthetic agent. 9 The present study directly assayed the amount of nitrite corresponding to nitric oxide production in macrophages. Our data shows that PPF does not influence nitric oxide production in untreated and in SNP-treated cells (Table I).…”