Pharmacologic characterization of meloxicam

Meloxicam provides a case study in the evolution of the cyclooxygenase (COX) hypothesis. Meloxicam was initially characterized in standard animal models of inflammation at a time when its improved pharmacologic profile in relation to other nonsteroidal anti-inflammatory drugs (NSAIDs) could not be explained. The subsequent discovery of COS-2 provided a reasonable working hypothesis. Meloxicam was investigated in several in vitro test systems in which it consistently demonstrated preferential COX-2 inhibition. These observations suggested that meloxicam would have a COX-1-sparing effect in vivo. Pharmacologic studies have confirmed the COX-1-sparing effect in animal models and in human subjects and suggest that the improved gastrointestinal and renal safety profile of this drugs may be related to this COX-2-sparing effect. The pharmacologic studies, taken together with the in vitro data, suggest the validity of the COX hypothesis as an estimator of NSAID efficacy and safety. Although further studies have suggested that meloxicam could affect inflammatory processes in other ways than by COX-2 inhibition, the clinical significance of these in vitro findings has yet to be determined. Moreover, accumulating evidence suggests a role for COX-2 in Alzheimer's disease and colorectal cancer. NSAIDs such as meloxicam could therefore be of potential benefit in the prevention or treatment of these diseases.