A dynamic model of once-daily 5-aminosalicylic acid predicts clinical efficacy.
New once daily mesalamine formulations may improve adherence to medication usage. Response to Asacol and other forms of 5-aminosalicyclic acid (5-ASA) is better correlated with tissue concentrations and best predicted by concentrations of the drug within the lumen of the colon. Our group used computer simulation to predict colonic 5-ASA levels after Asacol administration. In our study, the model simulated Asacol distribution in the healthy colon, and during quiescent and active ulcerative colitis. An Asacol dosage of 800 mg, three times a day, was compared to 2400 mg given once a day. Under ideal conditions, the predicted maximum drug in the total colon and individual colonic segments over 100 d differed by less than 3% between single and multiple doses. Despite changes in motility and defection rates, the predicted maximum and average 5-ASA concentrations in the total colon and individual colonic segments differed by less than 10% between dosing regimens. Asymmetric distribution of 5-ASA in the colon was influenced by frequency of bowel movements and colonic transit rate. In active colitis, sigmoid 5-ASA concentration becomes negligible. Our model supports once daily administration of Asacol as standard treatment for ulcerative colitis.
Parakkal
Deepak
D
Ehrenpreis
Eli D
ED
Thorpe
Matthew P
MP
Putt
Karson S
KS
Hannon
Bruce
B
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003106:Colon / Q000378:metabolism; D003198:Computer Simulation; D004334:Drug Administration Schedule; D006801:Humans; D019804:Mesalamine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008954:Models, Biological; D014018:Tissue Distribution; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine