BUCCAL AND COLONIC ABSORPTION OF CGS-16617, A NOVEL ACE INHIBITOR

The permeation of CGS 16617 -1S-pentyl)amino]-2,3,4,5-tetrahydro-2-oxo -3S-1H-1 benzazepine-1-acetic acid), a novel angiotensin converting en zyme (ACE) inhibitor, through isolated buccal and colonic mucosa in vi tro is described. In buccal mucosa, the flux was greatest in the dog, followed by the rabbit and pig, with similar time lags in all species. In the rabbit, the steady-state flux was linearly related to the dono r concentration which is indicative of diffusion as the absorptive mec hanism. Electrophysiological parameters were monitored to assess tissu e viability and, based on these parameters buccal mucosa may be classi fied as a moderately "tight" epithelium. The steady-state flux of CGS 16617 was 20- to 60-fold greater across colon compared to buccal mucos a. The steady-state flux of CGS 16617 across isolated colonic mucosa w as similar in the rat, rabbit and mini-pig, and about 2- to 3-fold hig her in the dog. In the rabbit and mini-pig, the flux was linearly rela ted to donor concentration. In both the rabbit and the rat, the flux w as inversely correlated with the electrical resistance of the tissue. Based on electrophysiological parameters, the colon is a moderately "l eaky" epithelium.