Pharmacokinetic Studies of 6-amidino-2-naphthyl 4-((4,5-dihydro-1H-imidazol-2-yl)amino) benzoate dimethanesulfonate (FUT-187). (1). Absorption, Distribution and Excretion 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 an ester of 4-[(4, 5-dihydro-1H-imidazol-2-yl)amino]benzoic acid (IABA) and 6-amidino-2-naphthol (AN). Absorption, distribution and excretion of FUT-187 were investigated in rats after single oral (1. 10. 30 and 100mg/kg) or intravenous (1 mg/kg) administration of [14C-IABA] FUT-187 or [14C-AN] FUT-187. 1. Blood levels of radioactivity (14C) after oral administration were higher in case of [14C-AN] FUT-187 administration, however, after intravenous administration, higher blood levels were observed in case of [14C-IABA] FUT-187. It was suggested, from the viewpoint of the different profiles of blood levels of 14C, that FUT-187 was easily hydrolized to its constituents by calboxvl-esterases. 2. Tissue distribution pattern of 14C was similar to the blood levels profiles. High levels of 14C were observed in the liver and kidney after oral administration of both forms of labeled FUT-187, but there was no evidence of accumulation of 14C in any tissues. 3. In general, urinary excretion of 14C after oral administration was higher in case of[14C-AN] FUT-187 administration, but the excretion ratio was not proportional to administered dose.4. The levels of 14C in the milk and fetuses were lower than those in the meternal blood.5. Binding of 14C to human, dog or rat serum albumins was about 10.2 ?? 35.2%.