Propofol: assay and regional mass balance in the sheep

1. Pharmacokinetic data for propofol, a new intravenous anaesthetic agent, indicate that there may be extensive extrahepatic clearance. This was investigated during intravenous infusions of propofol in adult merino ewes with chronic intravascular cannulae using a newly developed simple and rapid assay for propofol in blood and other biological samples. 2. The assay was based on organic solvent extraction of pH 4.5 buffered blood, urine or tissue homogenate, followed by reverse-phase h.p.l.c. with fluorescence detection. 3. A mean total body clearance of propofol of 3.15 l/min, (SD 0.87 l/min; n = 8) was found, consistent with a high hepatic extraction ratio (overall mean 0.87, SD 0.19; n = 8) and clearance (overall mean 1.12, SD 0.25 l/min; n = 7). The difference between total and hepatic clearances consisted principally of pulmonary clearance, but its extent was variable. 4. Other regional pharmacokinetic data were consistent with propofol distribution into muscle and brain tissues and propofol 'production' by the kidney, probably from a propofol metabolite formed elsewhere. 5. If these data are confirmed in humans then clinical pharmacokinetic data so far derived from peripheral venous blood sampling will require re-evaluation.