Pharmacokinetics of 5-[4-(2-Carboxyethylcarbamoyle) phenylaao] Salicylic Acid Disodium Salt Dihydrate (BX661A) (2) : Plasma Concentration and Metabolism in DSS-induced Ulcerative Colitis Model Rats

Abstract

The influence of diarrhea, which was the prime symptom of the ulcerative colitis, on pharmacokinetics of BX661A was investigated using DSS-induced ulcerative colitis model in rats.
1. After oral administration of ¹⁴C-BX661A or BX661A to model rats, plasma transitions of radioactivity and each compounds were similar to those of normal rats. Pharmacokinetics parameters also showed similar values.
2. After oral administration of BX661A to normal and model rats, the behavior of BX661A in gastrointestinal tract was similar in both rats. After administration of BX661A, the metabolites were hardly detected in the stomach and small intestine and more than 80% of the dose existed as unchanged drug at 2 hr after dosing. Whereas in caecum, the unchanged drug was recognized slightly, and 5-ASA, Ac-5-ASA, 4-ABA and Ac-4-ABA were abundant for the first 6-14 hr. In the large intestine, the unchanged drug was not detected over the observation time, and the contents of metabolites were maximal for the first 10 ?? 14 hr.