Extrahepatic morphine metabolism in man during the anhepatic phase of orthotopic liver transplantation.

The primary site for the metabolism of morphine has been the subject of controversy for some time. We studied morphine metabolism during the anhepatic phase of orthotopic liver transplantation in seven adult patients. After injection of morphine 10 mg at the beginning of this phase, the plasma and urinary concentrations of unchanged morphine, morphine-3-glucuronide, morphine-6-glucuronide and normorphine were measured by high pressure liquid chromatography. Small but measurable concentrations of morphine metabolites were found in the plasma and urine whilst there was no functional liver tissue in the body. Morphine metabolism increased markedly when the new donor liver was reperfused. This suggests that, in these patients, the liver is the primary site for metabolism of morphine.