Identification of urinary metabolites of ecabapide in rat

Abstract

1. ¹⁴C-Ecabapide, 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl]amino-N-methyl[¹⁴C]benzamide, was dosed orally to rat (100mg/kg). Within 48 h 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.