Drug metabolism and disposition : the biological fate of chemicals
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Drug Metab. Dispos. · May 1998
Intestinal absorption and stability of morphine 6-glucuronide in different physiological compartments of the rat.
Morphine 6-glucuronide (M6G) is an active metabolite of morphine that could be used as a drug, but its hydrolysis into morphine remains controversial. We investigated the acidic hydrolysis of M6G and found that the recovery of morphine did not exceed 5%. The stability of M6G was studied in different physiological compartments of male Sprague-Dawley rats. ⋯ An in vivo experiment demonstrated that after oral administration, M6G was absorbed per se in the proximal intestine, and the process was prolonged over the 24-hr experiment due to its reabsorption following enterohepatic recirculation. Finally, 10.5 +/- 4.3% of morphine and 12.9 +/- 5.1% of M3G compared with M6G AUCs were found in plasma. These results show that M6G is weakly converted into morphine when orally absorbed, with a kinetic profile similar to a slow release formulation.