PHARMACOLOGY OF MELOXICAM, A NEW NONSTEROIDAL ANTIINFLAMMATORY DRUG WITH AN IMPROVED SAFETY PROFILE THROUGH PREFERENTIAL INHIBITION OF COX-2

This review focuses on key pharmacological findings with a new NSAID, meloxicam. Unlike established NSAIDs, it preferentially inhibits induc ible COX-2 in guinea-pig peritoneal macrophages and human COX-2 in COS cells. Compared with other NSAIDs, meloxicam is the most potent inhib itor of prostaglandin biosynthesis in pleural and peritoneal exudate, but only a weak inhibitor in the gastric tract and kidney. Ulcerogenic ity in the rat stomach is weak in relation to anti-inflammatory potenc y, resulting in a high therapeutic index. Meloxicam's high anti-inflam matory potency combined with good tolerability can be explained by its preferential inhibition of COX-2. In adjuvant arthritis rats, meloxic am inhibits not only paw swelling, but also bone and cartilage destruc tion and systemic signs of disease. It inhibits leucocyte migration, b ut has no effect on leucotriene B4 or C4. Meloxicam shows a long-lasti ng anti-inflammatory and analgesic effect on inflammatory pain and red uces pyrogen-induced fever, but has no central nervous system effects. The pharmacokinetic profile of meloxicam in the rat is similar to tha t in man. Metabolites are inactive.