Clinical pharmacology of the selective COX-2 inhibitors

The discovery of two isoforms of cyclooxygenases (COX-1 and COX-2) has provided a new insight into the involvement of prostaglandins in the clinical effectiveness and gastrointestinal toxicity of NSAIDs. Currently, there are four selective COX-2 inhibitors available in Germany: celecoxib, rofecoxib, valdecoxib and parecoxib. Orally administered rofecoxib, celecoxib and valdecoxib have been approved for the relief of symptoms of osteoarthritis and rheumatoid arthritis. Parecoxib, the first selective COX-2 inhibitor for parenteral administration, has been approved for the short-term treatment of post-operative pain. The clinical efficacy of the marketed COX-2 inhibitors has been proved in large phase III clinical trials in comparison to both placebo and classical NSAIDs (e.g. diclofenac, naproxen). The incidence of gastrointestinal complications was significantly lower than that with the non-selective NSAIDs. However, the clinical relevance of these effects was, at least in some populations of patients (e.g. patients on low dose aspirin), not as high as initially expected. While not replacing less expensive classical NSAIDs, selective COX-2 inhibitors provide a marked enrichment of the spectrum of anti-inflammatory and analgesic therapeutics.