The cyclooxygenase-2 inhibitors: safety and effectiveness

To review the development of cyclooxygenase-2 (COX-2) inhibitors and discuss specific agents that are currently under investigation or have been marketed.

Primary literature on selective COX inhibitors was identified from a comprehensive MEDLINE, English-literature search from January 1966 through September 1998, with additional studies selected by review of the references. Abstracts from recent meetings and package insert literature from approved agents were also used as source material. Indexing terms included COX-2 inhibitors, meloxicam, celecoxib, rofecoxib, flosulide, SC-58635, and MK-966.

Human clinical, pharmacokinetic, and dose-ranging trials performed in Europe and the US and randomized comparative trials were reviewed.

With the discovery of at least two COX isoforms, a better understanding of the mechanism of action and gastrointestinal toxicity of nonsteroidal antiinflammatory drugs (NSAIDs) has been realized. While COX-1 is involved in physiologic maintenance, COX-2 seems to be involved in inflammation, mitogenesis, and specialized signal transductions. Selective COX-2 inhibitors may allow maximum antiinflammatory activity while improving the safety profile associated with NSAID therapy. Celecoxib and rofecoxib have been approved by the Food and Drug Administration for the treatment of osteo- and rheumatoid arthritis; meloxicam is undergoing Phase III clinical trials. Preliminary data indicate that the selective COX-2 inhibitors provide analgesic and antiinflammatory efficacy comparable with older NSAIDs, with fewer adverse gastrointestinal effects.

Specific COX-2 inhibitors offer promising benefits over older NSAIDs with regard to gastrointestinal safety while maintaining analgesic and antiinflammatory efficacy. Further study is required to determine long-term efficacy and safety in clinical use.