COX-2 inhibition with rofecoxib does not increase intestinal permeability in healthy subjects: a double blind crossover study comparing rofecoxib with placebo and indomethacin

Background-Acute and chronic use of non-steroidal anti-inflammatory drugs c an increase intestinal permeability. Rofecoxib, which selectively inhibits cyclooxygenase 2 (COX-2), is a novel antiinflammatory drug with the potenti al to produce minimal gastrointestinal toxic effects while retaining clinic al efficacy. Aims-To assess the potential for rofecoxib to affect the intestine adversel y, in comparison with placebo and indomethacin. Subjects-Thirty nine healthy subjects (aged 24-30 years). Method-We performed a four period crossover trial to assess intestinal perm eability before and after seven days of treatment. Permeability was measure d by the urinary ratio of chromium-51 labelled ethylene diamine tetraacetat e ((51)CrEDTA)/L-rhamnose (five hour collection). Results-Indomethacin 50 mg three times daily produced greater increases in intestinal permeability compared with placebo or rofecoxib (25 or 50 mg) (p less than or equal to 0.001); rofecoxib was not significantly different fr om placebo. Mean day 7 to baseline ratios (95% confidence intervals) for (5 1)CrEDTA/L-rhamnose were 0.97 (0.82, 1.16), 0.80 (0.68, 0.95), 0.98 (0.82, 1.17), and 1.53 (1.27, 1.85) for placebo, rofecoxib 25 mg, rofecoxib 50 mg, and indomethacin groups, respectively. Rofecoxib was generally well tolera ted. Conclusion-In this study, treatment for one week with indomethacin 50 mg th ree times daily significantly increased intestinal permeability compared wi th placebo, while treatment with rofecoxib 25 mg or 50 mg daily did not. Th e absence of a significant effect of rofecoxib on intestinal permeability a t doses at least twice those recommended to treat osteoarthritis was consis tent with other studies that have demonstrated little or no injury to the g astrointestinal mucosa associated with rofecoxib therapy.