Abstract
The biliary and urinary elimination of 3H-methadone and its metabolites was quantitatively studied after various routes of administration of the drug to rats. The biliary excretion products consisted largely of the N-demethylated metabolite of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and a highly water-soluble compound which is apparently a glucuronide conjugate of a hydroxylated derivative of EDDP. Phenobarbital pretreatment of rats was found to decrease the total excretion of EDDP in the bile, possibly through enhancement of another metabolic pathway, and at the same time to decrease the duration of narcosis resulting from the administration of methadone. Pretreatment with methadone was observed to greatly enhance the rate of biliary EDDP excretion in the first 4 hr after methadone administration.
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