Abstract

BACKGROUND
5-Aminosalicylate (5-ASA) formulations are approved for the treatment of ulcerative colitis (UC). Determination of the colonic pharmacokinetics of 5-ASA is challenging. A dynamic model of 5-ASA colonic amounts after oral delayed-release 5-ASA (Asacol), oral extended delayed-release 5-ASA (Lialda), 5-ASA enema (Rowasa), foam and suppositories (Canasa) was developed to determine the colonic kinetics of these agents.
METHODS
We created a model with Stella software. Colonic 5-ASA in the right, transverse, descending, sigmoid colon, and rectum were estimated for adults after recommended doses of the above formulations. Simulations of active mild/moderate UC and in remission were performed and compared using Student's t-test for differences in means.
RESULTS
For UC in remission, the highest amounts of 5-ASA were from Asacol in the right and transverse colon (P < 0.01), Lialda in the descending and sigmoid colon (P < 0.01), and Rowasa in the rectum (P < 0.01). For active UC, sigmoid amounts were highest with foam (P < 0.01), and rectal amounts highest with Rowasa (P < 0.01). Differences in rectosigmoid amounts of 5-ASA from enemas and suppositories for UC in remission occurred based on the relationship between the timing of administration relative to the daily bowel movement (P < 0.01).
CONCLUSIONS
Compared to Asacol, Lialda results in higher 5-ASA amounts in the left colon. Asacol with Rowasa provides highest 5-ASA amounts across the entire colon. Higher 5-ASA amounts from topical formulations occur when the insertion occurs soon after the daily bowel movement. This model provides a rationale for further investigation.

Links

Publisher Full Text

Authors

Stobaugh DJ, Deepak P, Thorpe M, Hannon B, Ehrenpreis ED

Institution

Gastroenterology Department, NorthShore University HealthSystem, Highland Park, Illinois, USA.

Source

Inflammatory bowel diseases 19:2 2013 Feb pg 301-8

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22644716