Pharmacology and pharmacokinetics of 5-aminosalicylic acid.

There is accumulating clinical evidence that 5-aminosalicylic acid (5-ASA), a primary metabolite of sulfasalazine (SAS), represents the therapeutic active moiety of the azo-compound SAS in the treatment of chronic inflammatory bowel disease (IBD). Since it is presumed that 5-ASA acts from the lumen of the intestine, it is important to know how much 5-ASA is released from its special galenic formulations. After liberation of 5-ASA in the terminal ileum (only slow release oral preparations of 5-ASA) and colon (5-ASA suppositories and enemas), 5-ASA is only partly absorbed. A major part of this 5-ASA is presystemically eliminated, eg, N-acetylated during its first passage through the intestinal mucosa and liver. Mean steady state plasma levels of unchanged 5-ASA are rather low (range 0.02 to 1.2 microgram/ml) whereas those of Ac-5-ASA are always higher (range 0.1 to 2.9 micrograms/ml). This is due to the rapid elimination of 5-ASA (t1/2 = 0.4 to 2.4h) and the slightly slower renal excretion of the Ac-5-ASA (t1/2 = 6 to 9 h, renal clearance = 200 to 300 ml/min). The knowledge of the pharmacokinetic properties of 5-ASA from different drug formulations might contribute to a better understanding of its mode of action in IBD.