[Significance of galenic preparations for luminal release of 5-aminosalicylic acid in human small intestinal lumen]

Abstract

Background: Sufficient intraluminal concentrations of 5-aminosalicylic acid (ASA) within inflamed regions of the intestine are required for therapeutic efficacy in inflammatory bowel disease. Various oral delayed release preparations have been developed to ensure that 5-ASA is set free in those parts of the gut, which are most frequently affected. However, resulting intraluminal concentrations within the small bowel are unknown. Therefore, we determined and compared 5-ASA release within different segments of the small bowel from an Eudragit L coated 5-ASA preparation (Salofalk) and from an ethylcellulose coated microsphere preparation (Pentasa).

Methods: Twelve healthy subjects were intubated with an oro-ileal multilumen-tube for marker perfusion, duodenal, jejunal and ileal aspiration of chyme and intestinal manometry. Each subject received 500 mg 5-ASA (Salofalk, n = 6, or Pentasa, n = 6) together with a semiliquid test meal. Intestinal aspirates, blood and urine samples were obtained in regular intervals for 7 to 10 hours and were analysed for 5-ASA and its main metabolite acetyl-5-ASA by HPLC.

Results: With Salofalk, gastric emptying of 5-ASA did not take place in the digestive, but in the subsequent interdigestive period. Luminal delivery of 5-ASA and acetyl-5-ASA increased from the duodenum (3% of dose) to the ileum (30% of dose). 10% of the dose administered were excreted in urine and about 90% reached the colon unreleased or solubilised. By contrast, with Pentasa, 5-ASA was delivered to the duodenum together with the test meal and released continuously throughout the small intestine (about 20% of dose solubilised at each intestinal site). Only 3.5% of the dose administered were excreted in urine. Deliver of 5-ASA to the colon was equal to Salofalk.

Conclusions: From both preparations, considerable amounts of 5-ASA are released during small intestinal transit thus explaining therapeutic efficacy in small intestinal Crohn's disease. Because of specific release patterns, Salofalk may be of use especially in terminal ileal disease, where as patients with extensive small intestinal disease including the proximal small intestine might benefit from Pentasa.