Background-Selective inhibitors of cyclooxygenase (COX)-2 may provoke less gastric damage and platelet inhibition than conventional non-steroidal antiinflammatory drugs. Aims-We compared the biochemical and gastrointestinal eVects of nimesulide, a potent and selective COX-2 inhibitor, with naproxen which exhibits no selectivity. 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 eVects were assessed by endoscopy, and by estimation of small intestinal absorptionpermeability and inflammation. Comparisons were made between variables at the end of each treatment phase. Results-Nimesulide caused significantly less gastric injury using the modified Lanza score (p<0.001) as well as reduced duodenum injury (p=0.039). Nimesulide 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 intestinal inflammation (5.5 (1.2) to 12.1 (2.1) mg/l) while nimesulide had no eVect (treatment diVerence p=0.03). Naproxen abolished platelet aggregation to arachidonic acid and suppressed serum thromboxane B 2 (TXB 2 ) by 98%, indices of COX-1 activity. In contrast, nimesulide had no significant eVect on platelet aggregation, although it reduced serum TXB 2 by 29%. Production of prostaglandin E 2 and prostacyclin by gastric biopsies, also COX-1 dependent, was inhibited by naproxen, but not by nimesulide. COX-2 activity, determined as endotoxin induced prostaglandin E 2 formation in plasma, was markedly 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. (Gut 2001;48:339-346)
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs and their widespread use is associated with increased gastro-intestinal toxic effects such as ulceration, haemorrhage, perforation and death. They result in these complications mainly by reducing cytoprotective prostaglandins (PGE2 and PGI2) in the stomach, through the inhibition of cyclo-oxygenase (COX) enzyme. The increased morbidity and mortality, in addition to enormous cost, associated with NSAID-associated side effects, necessitates a need for safer GI-friendly NSAID. Various approaches have been used to counteract NSAID associated side effects with varying degrees of success and acceptance. These include the use of alternative analgesia, anti-acid secretory agents like proton pump inhibitors, sucralfate and prostaglandin analogues. In addition, new types of NSAIDs are being developed, based on new understanding of their mechanism of action and the pathogenesis of inflammation. These include a new class of NSAIDs called "selective Cox-2 inhibitors". These agents preserve the COX-1 that is responsible for the production of cytoprotective prostaglandins in the stomach and selectively inhibit COX-2 induced at the sites of inflammation. Selective COX-2 inhibitors exert the same analgesic and anti-inflammatory effects as the existing NSAIDs but may be less toxic to the stomach. In this review the background development and well-structured clinical trials on this new generation NSAIDs are discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.