EXTRAHEPATIC METABOLISM OF PROPOFOL IN MAN DURING THE ANHEPATIC PHASE OF ORTHOTOPIC LIVER TRANSPLANTATION †

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Abstract
We have investigated extrahepatic metabolism of propofol in 10 patients undergoing orthotopic liver transplantation (group 1) (mean age 38 yr, mean weight 60 (SD 7) kg) and compared it with that in 10 patients without liver dysfunction undergoing extrahepatic abdominal surgery (group 2) (mean age 56 yr, mean weight 68 (11) kg). A single i.v. bolus dose of propofol 0.5 mg kg-1 was injected into a peripheral vein 5 min after the beginning of the anhepatic phase in group 1 and 60 min after the induction of anaesthesia in group 2. Arterial blood samples were obtained at 5, 10, 15, 20, 30, 40, 50 and 60 min after injection and urine samples were collected every 15 min. Propofol concentrations in whole blood and urine were measured by high performance liquid chromatography with fluorescence detection. Propofol glucuronide was measured in urine by incubation with a specific beta-glucuronidase. The area under the time-blood concentration curve from 0 to 60 min was found to be significantly greater in group 1 (13743 (2830) micrograms litre-1 h-1) than in group 2 (7992 (4895) micrograms litre-1 h-1) (P less than 0.05). Unchanged propofol was not detected in the urine of either group. No significant difference was found in the amount of propofol glucuronide excreted by patients in group 1 (457 (269) micrograms) and in group 2 (921 (672) micrograms). The presence of a propofol metabolite in urine when the liver was excluded from the circulation suggests that extrahepatic metabolism occurred.

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