JOURNAL ARTICLE

A dynamic model of colonic concentrations of delayed-release 5-aminosalicylic acid (Asacol)

M P Thorpe, E D Ehrenpreis, K S Putt, B Hannon
Alimentary Pharmacology & Therapeutics 2009 June 1, 29 (11): 1193-201
19222409

BACKGROUND: 5-ASA in a pH sensitive tablet (Asacol) is administered as three doses/day to treat ulcerative colitis. Once daily dosing may improve patient adherence. Simulation of colonic levels of 5-ASA can be used to compare dosing regimens.

AIM: To create a dynamic model of colonic concentrations of delayed-release 5-aminosalicylic acid (Asacol).

METHODS: Using published data, we created a computer model with STELLA software to simulate amounts of colonic 5-ASA in the total colon, right, transverse, descending and sigmoid/rectum after daily and three time/day Asacol.

RESULTS: The model predicted similar total and regional amounts of 5-ASA with both regimens. Distribution of 5-ASA was 38% in the right colon, 33% in the transverse colon and 14% each in the descending and sigmoid/rectal colon. Simulated increases in colonic motility and defecation rate exaggerated this 5-ASA distribution, resulting in negligible amounts of 5-ASA in the sigmoid/rectal region.

CONCLUSIONS: This computer model suggests that Asacol can be administered as a single daily dose. The model supports experimental and clinical observations that alternate dose or route of administration may be necessary to achieve adequate 5-ASA amounts in the distal colon during acute exacerbations of ulcerative colitis. This simulation cannot account for all sources of variability in the clinical setting, but provides a rationale for further investigation.

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