Meloxicam inhibits prostaglandin E(2) generation via cyclooxygenase 2 in the inflammatory site but not that via cyclooxygenase 1 in the stomach.

We studied the effects of meloxicam on prostanoid levels, both in the inflammatory site in rat carrageenin-induced pleurisy and in the rat stomach injected with 1 mol/l NaCl solution, to clarify the relationship between its low gastric toxicity and its relative cyclooxygenase (COX) 2 selectivity. NS-398 (3 mg/kg), a highly selective COX-2 inhibitor, and meloxicam (3 mg/kg) exhibited anti-inflammatory effects in the pleurisy model. Prostaglandin (PG) E(2) thromboxane (TX) B(2) and 6-keto-PGF(1alpha) were detectable in the inflammatory site. Anti-inflammatory doses of NS-398 and meloxicam each suppressed the intrapleural PGE(2) level at 5 h as potently as piroxicam (3 mg/kg) as aspirin (100 mg/kg), both of which are nonselective COX inhibitors. NS-398 was much less potent than the other three in suppressing the levels of TXB(2) and 6-keto-PGF(1alpha). These results suggest that PGE(2) may be produced mainly via COX-2 in this model and that meloxicam may inhibit COX-2 in the inflammatory site. Piroxicam completely inhibited the increase in gastric PGE(2) induced by administering 1 mol/l NaCl solution into the rat stomach. Nimesulide (3 mg/kg), another selective COX-2 inhibitor, however, never affected this increase, suggesting that the gastric PGE(2) may be produced via COX-1. The anti-inflammatory dose of meloxicam caused statistically nonsignificant suppression of the PGE(2) level, by approximately 50%. These results suggest that the potent anti-inflammatory effect of meloxicam, accompanied with low gastric toxicity, may be related to its relative selectivity for COX-2 over COX-1.