Parakkal D, Ehrenpreis ED, Thorpe MP, Putt KS, Hannon B. A dynamic model of once-daily 5-aminosalicylic acid predicts clinical efficacy. World J Gastroenterol 2010; 16(1): 136-137 [PMID: 20039462 DOI: 10.3748/wjg.v16.i1.136]
Corresponding Author of This Article
Eli D Ehrenpreis, Chief of Gastroenterology and Endoscopy, Highland Park Hospital, NorthShore University Health System and Clinical Associate Professor of Medicine, University of Chicago, 777 Park Avenue West, Highland Park, IL 60035, United States. ehrenpreis@gipharm.net
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World J Gastroenterol. Jan 7, 2010; 16(1): 136-137 Published online Jan 7, 2010. doi: 10.3748/wjg.v16.i1.136
A dynamic model of once-daily 5-aminosalicylic acid predicts clinical efficacy
Deepak Parakkal, Eli D Ehrenpreis, Matthew P Thorpe, Karson S Putt, Bruce Hannon
Deepak Parakkal, Department of Gastroenterology, NorthShore University Hospital, 2650 Ridge Ave Evanston, IL 60201-1718, United States
Eli D Ehrenpreis, Chief of Gastroenterology and Endoscopy, Highland Park Hospital, NorthShore University Health System and Clinical Associate Professor of Medicine, University of Chicago, 777 Park Avenue West, Highland Park, IL 60035, United States
Matthew P Thorpe, Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, United States
Karson S Putt, Department of Biochemistry, University of Illinois, Urbana, IL 61801, United States
Bruce Hannon, Department of Geography/NCSA, University of Illinois, Urbana, IL 61801, United States
Author contributions: Parakkal D, Ehrenpreis ED, Thorpe MP, Putt KS and Hannon B contributed equally to this work; All authors designed and performed the research; Thorpe MP, Putt KS, Hannon B contributed to the new analytic tools; All authors analyzed the data; Parakkal D and Ehrenpreis ED wrote the paper.
Correspondence to: Eli D Ehrenpreis, Chief of Gastroenterology and Endoscopy, Highland Park Hospital, NorthShore University Health System and Clinical Associate Professor of Medicine, University of Chicago, 777 Park Avenue West, Highland Park, IL 60035, United States. ehrenpreis@gipharm.net
Telephone: +1-847-6305398 Fax: +1-847-9265350
Received: November 8, 2009 Revised: November 25, 2009 Accepted: December 2, 2009 Published online: January 7, 2010
Abstract
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.
