Background:  Mesalamine provides topical anti-inflammatory action in the colon[k1] . Mesalamine is highly and rapidly absorbed in the intestine and thus, various delayed release mechanisms are used to prevent mesalamine from being absorbed until it reaches the colon. One example, Asacol¢ç delayed release (DR) tablets, is formulated by coating mesalamine with an acrylic-based resin that dissolves at pH 7 or greater. The variability in Asacol¢ç pharmacokinetics is high.  Recently DPA has evaluated the variability of Asacol¢ç in dissolution studies at pH conditions found in the gastrointestinal tract. Method:  Using a compartmental absorption and transit model for the intestine and the colon, we carried out absorption simulations of mesalamine. Data from IV, oral solution, and other mesalamine DR formulations determined the model parameters and their variabilities. Results: The distribution of AUC, Cmax, and Tmax were calculated using the observed variability of Asacol¢ç dissolution. Mean values of AUC, Cmax, and Tmax agree with the published results.  For each Asacol¢ç tablet, the location of drug absorption was identified and correlated with the observed pharmacokinetic parameters. Conclusions: Asacol¢ç is highly variable because of tablet to tablet variability in where the drug is released. When a tablet encounters pH 7 in the intestine, it dissolves rapidly, mesalamine is efficiently absorbed, and considerable plasma concentrations result. A tablet that does not encounter pH 7 until the colon results in less absorption and negligible plasma concentrations. This interaction between formulation performance and in vivo environment results in higher variability.