Selective inhibition of COX-2 in humans is associated with less gastrointestinal injury: a comparison of nimesulide and naproxen

Background-Selective inhibitors of cyclooxygenase (COX)-2 may provoke less gastric damage and platelet inhibition than conventional non-steroidal anti inflammatory drugs. Aims-We compared the biochemical and gastrointestinal effects of nimesulide , a potent and selective COX-2 inhibitor, with naproxen which exhibits no s electivity. Subjects-Thirty six healthy volunteers were randomised to nimesulide 100 mg or naproxen 500 mg twice daily for two weeks in a double blind, crossover study with a washout between treatments. Methods-Gastrointestinal side effects were assessed by endoscopy, and by es timation of small intestinal absorption-permeability and inflammation. Comp arisons were made between variables at the end of each treatment phase. Results-Nimesulide caused significantly less gastric injury using the modif ied Lanza score (p<0.001) as well as reduced duodenum injury (p=0.039). Nim esulide had lower visual analogue scores (VAS) for haemorrhage and erosive lesions in the stomach (p<0.001) and for mucosal injection in the duodenum (p=0.039). Naproxen increased excretion of calprotectin, a marker of intest inal inflammation (5.5 (1.2) to 12.1 (2.1) mg/l) while nimesulide had no ef fect (treatment difference p=0.03). Naproxen abolished platelet aggregation to arachidonic acid and suppressed serum thromboxane B-2 (TXB2) by 98%, in dices of COX-1 activity. In contrast, nimesulide had no significant effect on platelet aggregation, although it reduced serum TXB2 by 29%. Production of prostaglandin E-2 and prostacyclin by gastric biopsies, also COX-1 depen dent, was inhibited by naproxen, but not by nimesulide. COX-2 activity, det ermined as endotoxin induced prostaglandin E-2 formation in plasma, was mar kedly suppressed by both treatments. Interpretation-Nimesulide has preferential selectivity for COX-2 over COX-1 in vivo at full therapeutic doses and induces less gastrointestinal damage than that seen with naproxen in the short term.