Distribution in female rats of an anaesthetic intravenous dose of ¹⁴C-propofol

Abstract

1. Bolus i.v. doses of ¹⁴C-propofol (9 mg/kg) were administered to female rats for measurement of tissue levels of total ¹⁴C and propofol from 2 min to 24 h post-dose; whole-body autoradiography was studied at 6 min, 2h and 24 h post-dose, and also involved 15-day pregnant rats.

2. The blood propofol concentration-time profile was fitted by a tri-exponential function corresponding to a three-compartment open model. Data show rapid distribution during the mixing period into highly perfused tissues and muscle, comprising the central compartment, and slower uptake into less well-perfused skin and adipose tissues comprising the deeper compartments.

3. The initial decline in blood propofol concentration was associated with redistribution (t_1/2 4 min), the second decline (15–240 min post-dose) was associated with metabolism (t_1/2 33 min) and the third decline reflected slow depletion of drug from deep tissue compartments (t_1/2 6.4h).

4. Blood and brain propofol concentrations on waking (at 7 min post-dose) were 4 μg/ml and 9 μg/g respectively; the model shows that, at this time, 30% of the dose was lost from the central compartment by redistribution and a similar amount by metabolism.

5. Tissue profiles of total ¹⁴C and propofol diverged for highly perfused tissues (other than brain) because of slow clearance of metabolites, accentuated by enterohepatic recirculation.