Specific inhibition of cyclooxygenase-2 with MK-0966 is associated with less gastroduodenal damage than either aspirin or ibuprofen

Background: Compared with currently available NSAIDs (which inhibit COX-1 a nd COX-2 isoforms of cyclooxygenase), MK-0966 (a specific COX-2 inhibitor) is expected to cause less gastrointestinal toxicity. Aim: To compare the effect on the upper gastrointestinal mucosae of a high dose of MK-0966 with that of conventional doses of ibuprofen and aspirin. Methods: Healthy subjects (n = 170; age range 18-54 years) with endoscopica lly normal gastric and duodenal mucosa were randomized to either MK-0966 25 0 mg q.d. (n = 51), ibuprofen 800 mg t.d.s. (n = 51), aspirin 650 mg q.d.s. (n = 17), or placebo (n = 51) in this 7-day, double-blind, parallel-group study. The mucosae were evaluated by endoscopy using a predefined scale; sc ores could range from 0 to 4. The primary end-point was the percentage of s ubjects who developed a mucosal score greater than or equal to 2 (i.e. the development of one or more erosions). To evaluate COX-1 activity, serum thr omboxane B-2 levels were determined in a subset of the population. Results: The percentage of subjects who developed a mucosal score greater t han or equal to 2 in the MK-0966 group (12%) was significantly lower (P < 0 .001) than that in the ibuprofen (71%) and aspirin (94%) groups, and was si milar to that in the placebo group (8%). Only ibuprofen and aspirin signifi cantly (P < 0.0001) reduced baseline thromboxane B2 levels. All treatments were generally well tolerated. Conclusions: In this acute short-term endoscopic study, MK-0966 250 mg q.d. (a dose at least 10 times higher than that demonstrated to reduce the sign s and symptoms of osteoarthritis) produced significantly less gastrointesti nal mucosal damage than either ibuprofen 800 mg t.d.s. or aspirin 650 mg q. d.s. and was comparable to placebo in this regard.