Pharmacokinetic Studies of 6-Amidino-2-naphthyl 4-[(4, 5-dihydro-1 H-imidazol-2-yl)amino]benzoate dimethanesulfonate (FUT-187) (4) : Separatory Analysis of Intact FUT-187 and its Major Metabolites in 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). The metabolism of FUT-187 was studied after a single oral administration of [¹⁴C-IABA] FUT-187 or [¹⁴C-AN] FUT-187 to male rats at a dose of 30mg/kg.
1. Major metabolite of FUT-187 after oral administration of [¹⁴C-IABA] FUT-187 was IABA Dresent in the urine. feces and bile.
Only a small quantitiies of the unchanged FUT-187 were found in excreta. Minor metabolites, i.e., IABA glucuronide was found in urine.
2. Major metabolite of FUT-187 after oral administration of [¹⁴C-AN] FUT-187 were found to be AN-glucuronide and AN in the urine, feaces, bile, blood, liver, kidney and pancreas.
3. The concentrations of unchanged FUT-187, which is strongly related to its efficacy were 10 ?? 111 times higher in the liver, kidney, lung and pancreas than those in the blood.