Simulated comparison of topical and oral formulations of 5-aminosalicylate for the treatment of ulcerative colitis.
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.
Gastroenterology Department, NorthShore University HealthSystem, Highland Park, Illinois, USA.
Derrick J
DJ
Stobaugh
Parakkal
P
Deepak
Matthew
M
Thorpe
Bruce
B
Hannon
Eli D
ED
Ehrenpreis
D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003106:Colon / Q000378:metabolism*; D003198:Computer Simulation; D003692:Delayed-Action Preparations; D004733:Enema; D005772:Gastrointestinal Transit; D006801:Humans; D019804:Mesalamine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008954:Models, Biological; D012007:Rectum / Q000378:metabolism*; D012720:Severity of Illness Index; D013488:Suppositories
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D013488:Suppositories; D019804:Mesalamine