医薬品の生体内変化に関する研究(第83報)Morphine Glucuronidesのラットにおける代謝

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The metabolic fate of morphine 3-and 6-glucuronide was studied after the administration of these conjugates to rats by several routes. After the oral administration of either glucuronide, morphine, normorphine and the 3-glucuronide were identified in the urine, suggesting that both glucuronides were hydrolyzed in the gastrointestinal tract before absorption. The amount of total morphine excreted in the urine was larger after the oral administration of the 3-glucuronide, which has a lower Km value for β-glucuronidase than the 6-glucuronide, while the 6-glucuronide was thought to be more easily excreted in the bile than the 3-glucuronide because after subcutaneous or intravenous injection of the 6-glucuronide, the same metabolites as those obtained after the oral adninistration were detected in the urine, together with unchanged glucuronide. On the other hand, after subcutaneous injection of the 3-glucuronide, only a trace amount of free metabolites was excreted in the urine and major part of the metabolites was the 3-glucuronide. After intravenous injection of the 3-glucuronide, the urinary excretion rate of total morphine was raised, and more free morphine appeared in the urine, compared with two other administration routes. This hydrolysis of the glucuronide can be considcred to be induced when blood concentration of the glucuronide is high.
公益社団法人日本薬学会の論文
1975-05-25