Gastrointestinal Tolerability of the Selective Cyclooxygenase-2 (COX-2) Inhibitor Rofecoxib Compared With Nonselective COX-1 and COX-2 Inhibitors in Osteoarthritis

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Abstract
TWO ISOFORMS of cyclooxygenase (COX), COX-1 and COX-2,1-4 catalyze human prostaglandin synthesis. Almost all currently available nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both COX isoforms.5 COX-1 is constitutively expressed and generates prostaglandins believed to be involved in gastrointestinal (GI) mucosal protection,6 whereas COX-2 is induced at sites of inflammation throughout the body and generates prostaglandins that mediate inflammation and pain.7 Therefore, the anti-inflammatory effects of NSAIDs appear to be mediated via inhibition of COX-2,8 whereas the deleterious effects on the GI mucosa, which represent a significant source of morbidity and mortality, are believed to occur primarily via inhibition of COX-1.5 In addition, NSAIDs have been associated with a variety of upper GI tract symptoms, which may lead to switching NSAIDs, the use of concomitant medications for symptom relief, or discontinuation of NSAID therapy. Upper GI tract symptoms associated with NSAID use have generally not correlated well with mucosal damage or clinical events,9-13 and the roles of COX-1 and COX-2 in the pathogenesis of these symptoms are unclear.