CAPACITY-LIMITED GUT WALL METABOLISM OF 5-AMINOSALICYCLIC ACID, A THERAPEUTICALLY ACTIVE METABOLITE OF SULFASALAZINE, IN RATS

The metabolic fate of 5‐aminosalicylic acid (reported to be the active therapeutic moiety of sulfasalazine) was assessed in fasting rats as a function of dose (25 200 mg/kg) and administration route (oral, intraperitoneal, and intravenous). 5‐Aminosalicylic acid is subject to both capacity‐limited presystemic (apparently during first passage through the intestinal epithelium) and systemic acetylation. The possibility exists that 5‐aminosalicylic acid also is acetylated presystemically after oral sulfasalazine administration to patients with inflammatory bowel disease. Any alteration in the absorption rate of this active metabolite from the colon could affect the time course of local anti‐inflammatory activity if N‐acetyl‐5‐aminosalicylic acid is inactive or less active than 5‐aminosalicylic acid. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company