Disposition and pharmacology of propofol glucuronide administered intravenously to animals

Abstract

1. Propofol glucuronide (PG) is the major human metabolite of the i.v. anaesthetic propofol, 2,6-diisopropylphenol.

2. Bolus i.v. doses of ¹⁴C-PG (1mg/kg) to rat and dog were eliminated in urine (40 and 66% respectively) and faeces (48 and 19%); 25 and 48% of the dose were excreted unchanged in urine.

3. In dog, PG was distributed from plasma (t_1/2 4min) into a volume equivalent to extracellular water and eliminated with t_1/2 80 min. Total body clearance was 1.8 ml/min per kg, and renal clearance about 20% GFR. In rat, plasma ¹⁴C concentrations were about one-tenth those in dog, thus PG levels were not quantified.

4. Propofol was not detected in the plasma showing that PG is hydrolytically stable. Enterohepatic circulation of PG occurred in rat and to a lesser extent in dog. Metabolites, mainly side-chain hydroxylation products, were evident in both species from 4 h after dosing.

5. Bolus i.v. doses of PG (200 mg/kg) showed no hypnotic activity in mice.