抄録
The metabolic fate of morphine 3-and 6-glucuronide in rabbits, guinea pigs, and mice was studied. After the oral administration of either glucuronide to rabbits, the 3-glucuronide, morphine and a very small amount of the 6-glucuronide and normorphine were de tected in the urine. The 3-glucuronide, which has a higher affinity to β-glucuronidase, showed larger percentage recovery than the 6-glucuronide. Therefore, the urinary metabolites in this route were assumed to be derived from morphine which was liberated from the glucuronides in the gastrointestinal tract. After the subcutaneous injection to rabbits, however, only unchanged glucuronide and morphine were detected and no normorphine was found. These results suggested that the biliary system is not so important for the excretion of morphine glucuronides in rabbits. In addition, hydrolysis of these glucuronides seemed to proceed in the kidneys and/or bladder, from which liberated morphine would not be reabsorbed. This hydrolysis of the glucuronides could be considered to be induced when the blood concentration of the glucuronides was high enough, as already reported in the case of rats. Guinea pigs, to which the 6-glucuronide was subcutaneously injected, showed similar metabolism as rabbits. A small amount of the 3-glucuronide was detected besides the unchanged glucuronide and morphine in the urine of mice after subcutaneous injection of the 6-glucuronide. This suggested that a portion of the glucuronide would be excreted into the bile in mice, same as reported in the case of rats.
