Pharmacokinetic Studies of 6-Amidino-2-naphthyl 4-[(4, 5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate (FUT-187) (2) : Blood concentration, Distribution and Excretion after Consecutive 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). Blood concentration, distribution, excretion and accumulation of FUT-187 were investigated in male rats after consecutive oral administration of [¹⁴C-IABA] FUT-187 or [¹⁴C-AN] FUT-187 for 7 or 21 days.
1. During the consecutive oral administration of [¹⁴C-IABA] FUT-187 or [¹⁴C-AN] FUT-187 for 21 days, the blood radioactivity was constant at 1hr for [¹⁴C-IABA] FUT-187, at 3hr for [¹⁴C-AN] FUT-187 and at 24hr for both labelled forms of FUT-187 after each dosing.
After the consecutive oral administration of [¹⁴C-IABA] FUT-187 or [¹⁴C-AN] FUT-187 for 21days, blood level profiles were similar to those after a single administration.
2. After the consecutive oral administration of FUT-187, labelled at either position, for 21days, the total radioactivity in almost all organs decreased rapidly with similar patterns those observed after a single administration.
There was no clear indication of accumulation of FUT-187.
3. The excretion of radioactivity in the urine and feces was constant during consecutive oral administration of [¹⁴C-IABA] FUT-187 or [¹⁴C-AN] FUT-187 for 7days.
Within 8 days after the last dosing of [¹⁴C-IABA] FUT-187, 6.0% and 92.0% of administered radinactivity was excreted into the urine and feces. respectively.
In case of [¹⁴C-AN]FUT-187, 40.9% and 52.7% of the administered radioactivity excreted into the urine and feces, respectively.