PHARMACOLOGICAL CHARACTERIZATION OF MELOXICAM

Meloxicam provides a case study in the evolution of the cyclooxygenase (COX) hypothesis. Meloxicam was initially characterized in standard a nimal models of inflammation at a time when its improved pharmacologic profile in relation to other nonsteroidal anti-inflammatory drugs (NS AIDs) could not be explained. The subsequent discovery of COX-2 provid ed a reasonable working hypothesis. Meloxicam was investigated in seve ral in vitro test systems in which it consistently demonstrated prefer ential COX-2 inhibition. These observations suggested that meloxicam w ould have a COX-1-sparing effect in vivo. Pharmacologic studies have c onfirmed the COX-1-sparing effect in animal models and in human subjec ts and suggest that the improved gastrointestinal and renal safety pro file of this drug may be related to this COX-1-sparing effect. The pha rmacologic 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 a ffect inflammatory processes in other ways than by COX-2 inhibition, t he clinical significance of those in vitro findings has yet to be dete rmined. Moreover, accumulating evidence suggests a role for COX-2 in A lzheimer's disease and colorectal cancer. NSAIDs such as meloxicam cou ld therefore be of potential benefit in the prevention or treatment of these diseases.