Determination of the active moiety of BX661A, a new therapeutic agent for ulcerative colitis, by studying its therapeutic effects on ulcerative colitis induced by dextran sulfate sodium in rats.
5-[4-(2-Carboxyethylcarbamoyl)phenylazo]salicylic acid disodium salt dihydrate (CAS 80573-04-2, BX661A) is being developed as a therapeutic drug for ulcerative colitis. To determine the active therapeutic moiety of BX661A, the therapeutic effects with single and combined administration of 5-aminosalicylic acid (5-ASA), 4-aminobenzoyl-beta-alanine (4-ABA) and 4-amino-N-2-pyridinyl-benzenesulfonamide (CAS 144-83-2, sulfapyridine, SP) on ulcerative colitis induced by dextran sulfate sodium (DSS) in rats were investigated, and the following results were obtained. 1. BX661A at doses of 30, 100 and 300 mg/kg (p.o.) dose-dependently decreased the erosion area (mm2) in the large intestine with % inhibition values of 28.7, 49.1 and 61.6%, and the shortening of the large intestine with % inhibition values of 17.1, 25.7 and 48.6%, respectively. Salazosulfapyridine (SASP) at doses of 30 and 100 mg/kg (p.o.) decreased the erosion area (mm2) in the large intestine with % inhibition values of 30.7 and 45.3%, respectively, but did not improve the shortening of the large intestine. However, at a dose of 300 mg/kg (p.o.) SASP, the % inhibition value of the erosion area in the large intestine was reduced. 2. A single intrarectal administration of 5-ASA (105 mg/kg, i.r.) significantly decreased the erosion area (mm2) in the large intestine, but a single administration of 4-ABA or SP did not show any significant effect on the erosion area. Combined administration with 5-ASA (105 mg/kg, i.r.) and 4-ABA (142.8 mg/kg, i.r.) significantly decreased the erosion area (mm2) in the large intestine with a % inhibition value of 63.8%. On the other hand, the efficacy of 5-ASA disappeared with combined administration with SP (% inhibition value of 7.3%). These results suggest that 5-ASA is the active moiety for the therapeutic effects of BX661A and indicate that the efficacy of 5-ASA disappears with the combined use of SP, but not of 4-ABA. Therefore, it seems that BX661A is clinically safe and more effective than SASP in the treatment of patients with ulcerative colitis.[1]References
- Determination of the active moiety of BX661A, a new therapeutic agent for ulcerative colitis, by studying its therapeutic effects on ulcerative colitis induced by dextran sulfate sodium in rats. Kimura, I., Kawasaki, M., Nagahama, S., Matsuda, A., Kataoka, M., Kokuba, Y. Arzneimittel-Forschung. (1998) [Pubmed]
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