Identification of urinary metabolites of ecabapide in rat.

1. 14C-Ecabapide, 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl]amino-N- methyl[14C]benzamide, was dosed orally to rat (100 mg/kg). Within 48h after dosing, 36.7 +/- 5.4 and 55.7 +/- 11.8% of the administered radioactivity was recovered from urine and faeces respectively. 2. The unchanged drug was the major compound excreted in the urine and accounted for 37% of the urinary radioactivity. Seven urinary metabolites were purified by preparative hplc and their structures were elucidated by mass and 1H-nmr spectrometry. 3. The major metabolic pathway of ecabapide was found to be the formation of 3-amino-N-methylbenzamide produced by N-dealkylation of the secondary amine at the 3-position of the benzamide moiety followed by acetylation. 4. Further metabolic pathways of the N-methylbenzamide moiety were N-demethylation via the carbinolamine derivatives, and/or aromatic hydroxylation followed by glucuronidation.