Selective prostaglandin biosynthesis inhibition of zaltoprofen at the inflammatory site

Abstract

Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the production of primary prostanoids by blocking both cyclooxygenase (COX) -1 and COX-2 activities, and in doing so, not only decrease inflammation and pain, but also promote gastrointestinal tract damage and bleeding.The inhibitory activities of zaltoprofen (ZP) on the biosynthesis of prostaglandin E2 (PGE2) at the inflammatory site and stomach were compared with those of some NSAIDs (celecoxib : CL, meloxicam : ML, lornoxicam : LR, mofezolac : MF) using the rat carrageenin-air pouch model. At the dose of ZP and CL that inhibited PGE2biosynthesis at the inflammatory site, these hardly inhibited the PGE2release from stomach. In contrast, ML, MF and LR inhibited the biosynthesis of PGE2on both sites at the same dose.Furthermore these NSAIDs inhibited the carrageenin-induced paw edema, and produced the ulcer in a dose-dependent manner. The safety index, UD50/ED40ratio, of CL, ZP, ML, LR and MF was >103, 11.3, 0.8, 0.8 and 0.1, respectively. These safety indexes correlated well with the tissue selectivity of NSAIDs on PG biosynthesis inhibition.These results suggest that the PG biosynthesis at the inflammatory site and stomach of the same rat is a very useful parameter for evaluating NSAIDs. It seems that these properties of ZP were contributed to the low ulcerogenic activity on clinical uses.