Pharmacokinetic Studies of 6-Amidino-2-naphthyl 4-((4,5-dihydro-1H-imidazol-2-yl)amino)benzoate dimethanesulfonate (FUT-187). (3). Whole-body Autoradiography after a Single Oral Administration to Rats.

Abstract

6-Amidino-2-naphthyl 4-[(4, 5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate (FUT-187), a novel protease inhibitor, is a ester of 4-[(4, 5-dihydro-1H-imidazol-2-yl)amino]benzoic acid (IABA) and 6-amidino-2-naphthol (AN). During the course of the studies on the physiological disposition of FUT-187 in rats, the tissue distribution of radioactivity in albino male, pregnant and pigmented male rats after a single oral administration of [14C-IABA] FUT-187 or [14C-AN] FUT-187 (30mg/kg) was investigated by wholebody autoradiographv (WARG). 1. In both cases of administration of[14C-IABA]FUT-187 and [14C-AN] FUT-187, WARG showed high levels of radioactivity in the kidney, liver, skin, epididymis, submaxillary gland, aorta and esophagus. WARG at 24hr after oral administration of FUT-187 labelled at either position showed that radioactivity remained only in the intestinal contents and urine present in the bladder. 2. In female rats on day 13 and 19 of gestation, much lower levels of radioactivity were observed, indicating a difficult passage through the placenta into the fetuses after oral administration of FUT-187 labelled at either position. 3. WARG of pigmented male rats after oral administration of FUT-187 labelled at either position showed that the radioactivity was not specifically distributed to any tissues.