The Disposition, Tissue Distribution, and Cellular Transport of N[[(Trimethylamino)boryl]carbonyl]-L-phenylalanine Methyl Ester in CF1 Mice

Abstract

The disposition and tissue distribution of14C-labeledN-[[(trimethylamino)boryl]carbonyl]-l-phenylalanine methyl ester (1) was determined in CF1mice following iv, po, and ip administration. Compound1was found to undergo rapid and extensive metabolism, and the majority of the radioactivity was found in the skin and carcass regardless of the route of administration. Approximately 55% of the radioactivity was recovered in urine and feces after 78 h; however, excretion via these routes was not complete. Degradation of compound1occurred at the amide bond at low pH (0.8) but at the ester bond a physiological pH. This difference in degradation was reflected in elevation of the blood radioactivity levels after po administration compared to ip and iv administration.