Pharmacology of meloxicam, a new non-steroidal anti-inflammatory drug with an improved safety profile through preferential inhibition of COX-2.
This review focuses on the key pharmacological findings with a new NSAID, meloxicam. Unlike established NSAIDs, it preferentially inhibits inducible COX-2 in guinea-pigs peritoneal macrophages and human COX-2 in COS cells. Compared with other NSAIDs, meloxicam is the most potent inhibitor of prostaglandin biosynthesis in pleural and peritoneal exudate, but only a weak inhibitor in the gastric tract and kidney. Ulcerogenicity in the rat stomach is weak in relation to anti-inflammatory potency, resulting in a high therapeutic index. Meloxicam's high anti-inflammatory potency combined with good tolerability can be explained by its preferential inhibition of COX-2. In adjuvant arthritis rats, meloxicam inhibits not only paw swelling, but also bone and cartilage destruction and systemic signs of disease. It inhibits leucocyte migration, but has no effect on leucotriene B4 or C4. Meloxicam shows a long-lasting anti-inflammatory and analgesic effect on inflammatory pain and reduces pyrogen-induced fever, but has no central nervous system effects. The pharmacokinetic profile of meloxicam in the rat is similar to that in man. Metabolites are inactive.
Engelhardt
G
G
Dr Karl Thomae GmbH, Department of Biological Research, Biberach/Riss, Germany.
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004361:Drug Tolerance; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D000077239:Meloxicam; D051379:Mice; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced; D013843:Thiazines / Q000009:adverse effects / Q000494:pharmacology*; D013844:Thiazoles / Q000009:adverse effects / Q000494:pharmacology*
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam