Pharmacokinetics of 5-[4-(2-Carboxyethylcarbamoyle)-phenylazo] Salicylic Acid Disodium Salt Dihydrate (BX661A) (4): Plasma Concentration, Distribution, Metabolism and Excretion in Rat after Repeated Oral Administration

Pharmacokinetics of BX661A was investigated following 7-day or 14-day period of daily oral administration of 14C-BX661A(14C-BX661A(5ASA): labeled at 5ASA moiety, 14C-BX661A(4ABA): labeled at 4ABA moiety) and non-labeled BX661A to male rats. 1. Two metabolites, acetyl-p-aminobenzoic acid and acetyl-p-amino-hippuric acid were found in the urine. 2. After repeated oral administration of 14C-BX661A(5ASA) to rats, no differences were observed in Cmax, AUC and Tmax between the 1st, 7th and 14th dose. While after repeated oral administration of 14C-BX661A(4ABA) to rats, plasma level of radioactivity at 24 hr after the 7th dose was increased to more than 15 times of the 1st dose. But Cmax, AUC and Tmax of 14th dose were almost equal to those of 7th dose. 3. The plasma transition of BX661A and its metabolites did not change during 14-day period of daily oral administration of BX661A. At 24 hr after every dosing, plasma concentrations of BX661A and its metabolites were not detectable or were close to the limit of detection. 4. After repeated oral administration of 14C-BX661A(5ASA) to rats, tissue radioactivity levels at 24 hr after the 7th dose increased to about 2 times of the 1st dose, but the levels after the 14th dose were almost equal to those of 7th dose. After the final dose, the radioactivity in all tissues was decreased slowly and the accumulation was not observed. 5. After repeated oral administration of 14C-BX661A(4ABA) to rats, tissue radioactivity levels at 24 hr were increased with dosing. However, the ratios of tissue/plasma concentration were unchanged in all tissues tested. After final dose, the elimination of radioactivity from all tissues were slower than that of plasma. 6. The excretion pattern of BX661A and its metabolites into urine and feces were almost constant during the repeated oral administration.