Acute gastrointestinal permeability responses to different non-steroidal anti-inflammatory drugs

Background and aims-Non-steroidal anti-inflammatory drugs (NSAIDs) cause ga strointestinal damage both in the upper and lower gastrointestinal tract. N ew antiinflammatory drugs have been developed in an attempt to improve thei r gastrointestinal side effect profile., Our objective was to compare the, effect on gastrointestinal permeability of acute equieffective doses of fou r different NSAIDs; three were designed to reduce gastrointestinal mucosal injury. Materials-Healthy volunteers underwent sugar tests in a randomised fashion, 15 days apart, at: (1) baseline; (2) after two days of 75 mg slow release (microspheres) indomethacin; (3) after two days of 7.5 mg oral meloxicam wh ich preferentially inhibits cyclooxygenase 2; and (4), after two days of 75 0 mg naproxen. A subgroup of subjects was tested after two days of 200 mg c elecoxib. In each test, subjects ingested a solution containing sucrose, la ctulose, and mannitol and sucralose, to evaluate gastroduodenal, intestinal , and colonic permeability, respectively. Results-Gastric permeability was significantly affected by naproxen (p < 0. 05) but not by slow release indomethacin, meloxicam, or celecoxib. Intestin al permeability was significantly increased by the first three NSAIDs (p < 0.05) but not by celecoxib. Abnormal lactulose/mannitol ratios were observe d in 42% of meloxicam treatments, in 62% during indomethacin, and in 75% of subjects treated with naproxen. Finally, colonic permeability, as measured by sucralose, was not significantly increased by any of the four drugs. Conclusion-Our study provides evidence that the newly developed NSAIDs redu ce gastric mucosal permeability significantly. However, most produced signi ficant alteration of small intestinal permeability. In contrast, our result s, suggest that celecoxib seems to exhibit the most desirable gastrointesti nal side effect profile..