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


OBJECTIVE
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.
Thorpe
M P
MP
Division of Nutritional Sciences, University of Illinois, Urbana, IL, USA.
Ehrenpreis
E D
ED
Putt
K S
KS
Hannon
B
B
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003106:Colon / Q000378:metabolism*; D003198:Computer Simulation; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D006801:Humans; D019804:Mesalamine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008954:Models, Biological; D010349:Patient Compliance; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D019804:Mesalamine