The coxibs, selective inhibitors of cyclooxygenase-2

Drug TherapyALASTAIR J.J. WOOD, M.D., EditorDRUG THERAPYN Engl J Med, Vol. 345, No. 6·August 9, 2001·www.nejm.org·433THE COXIBS, SELECTIVE INHIBITORSOF CYCLOOXYGENASE-2GARRET A. FITZGERALD, M.D., AND CARLO PATRONO, M.D.From the Center for Experimental Therapeutics, University of Pennsyl-vania, Philadelphia (G.A.F.); and the Department of Medicine and Centerof Excellence on Aging, University of Chieti, Chieti, Italy (C.P.). Addressreprint requests to Dr. FitzGerald at the Department of Pharmacology, 153Johnson Pavilion, 3620 Hamilton Walk, University of Pennsylvania, Phila-delphia, PA 19104-6084, or at [email protected] antiinflammatory drugs(NSAIDs) are widely used to treat arthritis,menstrual pain, and headache. Although theyare effective, their long-term use is limited by gas-trointestinal effects such as dyspepsia and abdominalpain and, less often, gastric or duodenal perforationor bleeding. Development of the coxibs, a new groupof antiinflammatory drugs, represents a response tothe unsatisfactory therapeutic profile of NSAIDs. Bothgroups of drugs inhibit prostaglandin G/H synthase,the enzyme that catalyzes the transformation of arach-idonic acid to a range of lipid mediators, termedprostaglandins and thromboxanes (Fig. 1). However,whereas NSAIDs inhibit the two recognized forms ofthe enzyme, also referred to as cyclooxygenase-1 andcyclooxygenase-2, the coxibs are selective inhibitorsof cyclooxygenase-2. The inhibition of cyclooxygen-ase-2 has been more directly implicated in ameliorat-ing inflammation, whereas the inhibition of cycloox-ygenase-1 has been related to adverse effects in thegastrointestinal tract. Therefore, it was hoped thatcoxibs would be better tolerated than nonselectiveNSAIDs but equally efficacious. This review will as-sess the evidence that has emerged in support