IDENTIFICATION OF MAJOR BILIARY AND URINARY METABOLITES OF ECABAPIDE IN RATS

1. The structures of major biliary and urinary metabolites of ecabapid e in rat were identified by comparison with authentic standards using lc-ms and H-1-nmr spectrometry. 2. A major metabolite was found in the bile obtained from rat after an oral dose of C-14-ecabapide and ident ified as the amidaldehyde derivative. In the urine, two polar metaboli tes were characterized as the phenolic sulphates. Further, two lipophi lic metabolites were identified as alcohol derivatives, and two others as oxamic acids. 3. From these results, it was estimated that the fir st step in the metabolism of ecabapide in rat was oxidative N-dealkyla tion to produce the amidaldehyde. This amidaldehyde was further metabo lized by two routes, one by reduction of the amidaldehyde into the cor responding alcohol followed by mono-demethylation and subsequent aroma tic O-sulphation, the second by oxidation of the amidaldehyde into the oxamic acid followed by mono-demethylation and subsequent aromatic O- sulphation.