PT  - JOURNAL ARTICLE
AU  - S. Y. Zhou
AU  - D. Fleisher
AU  - L. H. Pao
AU  - C. Li
AU  - B. Winward
AU  - E. M. Zimmermann
TI  - Intestinal Metabolism and Transport of 5-Aminosalicylate
DP  - 1999 Apr 01
TA  - Drug Metabolism and Disposition
PG  - 479--485
VI  - 27
IP  - 4
4099  - http://dmd.aspetjournals.org/content/27/4/479.short
4100  - http://dmd.aspetjournals.org/content/27/4/479.full
SO  - Drug Metab Dispos1999 Apr 01; 27
AB  - The purpose of this study was to determine the characteristics of intestinal absorption and metabolism of 5-aminosalicylic acid (5ASA). Regional perfusions of 5ASA in the anesthetized rat resulted in the appearance of N-acetyl-5-aminosalicylic acid in the intestinal lumen. Lumenal metabolite appearance was proportional to 5ASA permeability, which was 5-fold higher in the jejunum than in the ileum. Intestinal elimination significantly decreases 5ASA absorption at low lumenal drug concentrations and this process is saturated at high drug concentrations. Metabolite levels in intestinal tissue were higher than plasma levels at low perfusion drug concentrations, whereas the reverse was observed at high concentrations. Transport and metabolism of 5ASA was studied in Caco-2 monolayers. At low drug concentrations, 5ASA was preferentially transported in the basolateral (BL) to apical (AP) direction. With 5ASA incubation in either the AP or BL chamber, the N-acetyl metabolite appeared only in the AP compartment. Transport ofN-acetyl-5-aminosalicylic acid was also exclusively observed in the BL to AP direction. Clinical data indicate that anti-inflammatory response to oral 5ASA correlates with the amount of 5ASA delivered to the intestinal tissue. This study shows that at lumenal levels below 200 μg/ml (concentrations that are typically achieved by controlled release dosage forms), intestinal secretion of 5ASA accounts for more than 50% of the total elimination and can significantly affect tissue levels and, therefore, may be an important factor in determining the response to 5ASA therapy. The American Society for Pharmacology and Experimental Therapeutics