The metabolism of trimebutine maleate (I), (±)-2-demethylamino-2-phenylbutyl 3, 4, 5-trimethoxybenzoate hydrogen maleate, was studied in dogs and man after oral administration of 14C-labeled I to beagle dogs and of nonlabeled I to human volunteers. Metabolites of I in the urine and plasma were fractionated, identified and quantified.
In both species, I was rapidly metabolized and the main urinary metabolites were alcoholic and acidic products of ester hydrolysis, N-demethylated metabolites, and conjugates : i. e., 2-dimethylamino-2-phenylbutanol (II) and its N-mono and di-demethylated metabolites (II and IV), 3, 4, 5-trimethoxybenzoic acid (V), and their conjugates. In dogs, most of the alcohol-moiety metabolites (III ≥ II > II, 60.1%) were excreted in conjugated from and the acid-moiety metabolite (V, 46.5%) in unconjugated form. In man, N-mono- and di-demethylated metabolites (VI, VII) of I retaining the ester bond were detected in a total amount corresponding to 0.3% of the administered dose. The alcohol-moiety metabolites (IV > III > II, 62.1 %) were excreted in both unconjugated (28.4%) and conjugated form (33.7%). The acid-moiety metabolite (V, 50.9%) was mainly excreted as the glucuronic acid conjugate (41.2 %) and only partly in unconjugated form (9.7%). In plasma, I and its N-demethylated metabolites (V1, VII) were detected in both species beside the urinary metabolites. Main plasma metabolites were V and the conjugates of the alcohol-moiety metabolites in dogs, and V and one (VI) of the demethylated metabolites of I in man.
