Measurement of in vivo Gastrointestinal Release and Dissolution of Three Locally Acting Mesalamine Formulations in Regions of the Human Gastrointestinal Tract

• DOI: 10.1021/acs.molpharmaceut.6b00641
• Publication Date: 2016-12-25T03:54:18Z
• Authors: Alex Yu; Jason R. Baker; Ann F. Fioritto; Ying Wang; Ruijuan Luo; Siwei Li; Bo Wen; Michael Bly; Yasuhiro Tsume; Mark J. Koenigskn...; Xinyuan Zhang; Robert Lionberger; Gordon L. Amidon; William L. Hasler; Duxin Sun
• Keywords: Jejunum

As an orally administered, locally acting gastrointestinal drug, mesalamine products are designed to achieve high local drug concentration in the (GI) tract for treatment of ulcerative colitis. The aim this study was directly measure and compare dissolution three formulations human GI correlate their with plasma. Healthy subjects were administered Pentasa, Apriso, or Lialda. fluids aspirated from stomach, duodenum, proximal jejunum, mid distal jejunum regions. Mesalamine (5-ASA) its primary metabolite acetyl-5-mesalamine (Ac-5-ASA) measured using LC–MS/MS. pH each fluid sample, which averaged 1.82, 4.97, 5.67, 6.17, 6.62 middle respectively. For levels 5-ASA solution observed 1 7 h. Apriso had minimal low medium duodenum 4 h, 3 In contrast, Lialda stomach early small intestine. A composite appearance rate (CAR) calculated deconvolution individual plasma reflect release, dissolution, transit, absorption tract. Individuals dosed Pentasa CAR 10 h; individuals h 5 showed 0 then increased 12 decreased further lower after colon region, similar accumulated excreted feces, while slightly higher accumulation feces. However, all Ac-5-ASA These results provide direct measurement tract, can serve as a basis investigation bioequivalence products.