ABSORPTION, ENTEROHEPATIC CIRCULATION, AND EXCRETION OF 5-AMINOSALICYLIC ACID IN RATS

Abstract

After oral administration of sulfasalazine, the majority of the administered dose reaches the colon, where it is split into 5-aminosalicylic acid (5-ASA) and sulfapyridine. 5-ASA is believed to be the effective component in the treatment of inflammatory bowel disease. After intraduodenal administration of 5-ASA (20 mg) in rats, 91% of the drug was absorbed in the proximal small intestine. Peak serum 5-ASA concentration (55 .mu.g/ml) was reached in 1 h. Approximately 61 and 6% of the administered dose were excreted in the urine and bile, respectively, in 24 h, almost exclusively in the acetylated form. When sulfapyridine (20 mg) was administered in addition to 5-ASA, 70% of the sulfapyridine was absorbed in the small intestine, peak serum concentration (50 .mu.g/ml) was reached in 1 h and 30% of the administered dose was excreted in the urine in 24 h. After oral administration of 5-ASA, a therapeutically significant concentration of the drug is not expected in the terminal ileum, which is a common site of involvement in Crohn''s disease. The therapeutic implications of these findings are discussed herein.