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

M. P. Thorpe, E. D. Ehrenpreis, K. S. Putt, B. Hannon

Research output: Contribution to journalArticle

Abstract

Backround 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.

Original languageEnglish (US)
Pages (from-to)1193-1201
Number of pages9
JournalAlimentary Pharmacology and Therapeutics
Volume29
Issue number11
DOIs
StatePublished - Jun 1 2009

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

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