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  • Title: Enterohepatic circulation of l-alpha-acetylmethadol in the rat.
    Author: Roerig DL, Hasegawa AT, Wang RI.
    Journal: J Pharmacol Exp Ther; 1980 May; 213(2):284-8. PubMed ID: 7365687.
    Abstract:
    The enterohepatic circulation of the biliary metabolites of l-alpha[3H]acetylmethadol ([3H]LAAM) was studied in rats. Bile was collected for 48 hr from a biliary-cannulated donor rat after s.c. administration of [3H]LAAM. This bile containing tritium-labeled LAAM metabolites was then infused into the small intestine of a recipient rat for 48 hr and the appearance of radioactivity in bile formed in the liver of the recipient rat was monitored. Forty-eight hours after the start of infusion, 40% of the infused radioactivity had been excreted into the bile of the recipient rat, indicating extensive enterohepatic circulation of the biliary metabolites of LAAM. The data indicated that only a small percentage of the infused [3H]LAAM metabolites were present in the systemic circulation at any one time. This was further investigated by comparing the plasma levels of tritium with time and the tissue concentrations at 24 and 48 h after s.c. [3H]LAAM administration in biliary-cannulated and sham-operated control rats. Complete diversion of the bile did not significantly decrease the levels of [3H]LAAM or its metabolites in the systemic pool. These findings tend to minimize the contribution of enterohepatic circulation in the recirculation of active metabolites of LAAM and ultimately in its long duration of opiate-like action.
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