Glucuronidation of Morphine in Human Liver and Interaction with Oxazepam

Morphine is primarily metabolized through glucuronidation by a microsomal UDP-glucuronyltransferase. With the use of 14C-morphine the activity of this enzyme was measured in hepatic microsomes from ten kidney transplant donors with total cerebral infarction and four icteric patients with pancreatic carcinoma. In the former livers the rate of glucuronidation varied from 1.08 to 8.67 nmol per mg microsomal protein per min, with a mean value of 3.83. These values were somewhat higher than in the liver biopsies from the four cancer patients. Oxazepam, at 1/10 the concentration of morphine, inhibited the morphine glucuronidation by 35%. The inhibition was competitive. Salicylamide also inhibited the morphine glucuronidation but only at concentrations considerably higher than morphine. The relevance of the in vitro data for the in vivo situation is unclear, since the concentrations employed in this study are several-fold higher than those encountered in the plasma of patients treated with these drugs.