Inhibition of morphine glucuronidation by oxazepam in human fetal liver microsomes.

Uridine diphosphoglucuronyltransferase activity toward morphine was measured in vitro in preparations of human fetal liver microsomes. The inhibition of the glucuronidation of morphine was studied at concentrations of morphine and uridine diphosphoglucuronic acid of 3 and 15 mM, respectively. Oxazepam inhibited the reaction by about 50% at concentration of 0.3 mM. The inhibition was almost complete when the concentration was 3 mM, i.e., the same as for morphine. Salicylamide was considerably less potent as an inhibitor of morphine glucuronidation with an almost 100-fold difference in potency as compared to oxazepam. Lineweaver-Burk plots of the inhibition data revealed that oxazepam exerts a competitive type of inhibition with an apparent Ki value of 0.2 mM.