Clinical review of rofecoxib a cox-2-specific inhibitor in the treatment of pain and arthritis

Journal/Book: Z Rheumatol 1999; 58: 369. 1999;

Abstract: G. Bell; M. D Merck and Co lnc. Highland Park Prostaglandins are important mediators of pain and inflammation. It is currently understood that prostaglandin synthesis in humans is catalyzed by at least two isoforms of cyclooxygenase (COX) COX-1 and COX-2 (otherwise referred to as prostaglandin synthase 1 and 2). COX-1 is constitutively expressed throughout the body whereas COX-2 expression is induced by a variety of mediators including growth factors cytokines and mitogens. The two COX isoforms have different subcellular locations and may utilize different phospholipase systems and/or arachidonic acid stores. Given the localization and pattern of induction of the two COX isoforms it is hypothesized that COX-2 is primarily responsible for the synthesis of prostanoids that mediate responses to pathological processes such as pain inflammation and fever whereas in the gastrointestinal tract and in platelets COX-1 is primarily responsible for the synthesis of prostanoids that protect the GI mucosa and mediate platelet aggregation. NSAIDs such as ibuprofen naproxen and indomethacin inhibit both cyclooxygenase (COX) isoforms: COX-1 and COX-2. The clinical benefits of NSAIDs are believed to be derived from their inhibition of COX-2 whereas the GI and platelet toxicities are believed to be due to the inhibition of COX-1. Rofecoxib has been characterized as a specific inhibitor of COX-2 by ex vivo assays of COX inhibition in humans. Consistent with its COX-2 specificity rofecoxib did not inhibit platelet-mediated thromboxane production or platelet aggregation and did not alter bleeding time even when administered at doses well above the clinical dose range. In clinical studies in osteoarthritis (12.5 to 25 mg once daily) and in three separate acute pain models (50 mg once daily) specific inhibition of COX-2 with rofecoxib was as effective as comparator NSAIDs across primary and secondary efficacy endpoints. ... le

Zurück | Weiter