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The effects of meloxicam, indomethacin or NS-398 on eicosanoid synthesis by fresh human gastric mucosa

, : The effects of meloxicam, indomethacin or NS-398 on eicosanoid synthesis by fresh human gastric mucosa. Alimentary Pharmacology & Therapeutics 14(6): 795-799, June

Background: In the stomach, constitutive cyclooxygenase (COX-1) synthesizes prostaglandins that maintain the integrity of the gastric mucosa, while their inhibition contributes to gastric mucosal damage. In contrast COX-2, an inducible enzyme, forms prostanoids involved in pain and inflammation. Aim: To compare prostaglandin synthesis inhibition by meloxicam, a selective COX-2 NSAID reported to have better gastric tolerability, with indomethacin and NS-398 in human gastric mucosa and in whole blood assays. Methods: Meloxicam, indomethacin or NS-398 were incubated with fresh human gastric mucosa pieces (100 mg in 1 mL phosphate buffered saline, pH 7.4, 37 degreeC, 30 min), clotting human blood (1 mL, 37 degreeC, 60 min) or with lipopolysaccharide-stimulated heparinized blood (1 mL, 37 degreeC, 24 h). Prostanoids were analysed by radioimmunoassay. Results: Meloxicam was a less potent inhibitor of gastric mucosal eicosanoid compared to indomethacin, showing a sixfold difference in IC50 with gastric mucosal prostaglandin E (PGE) (11.8 and 1.8 muM, respectively). In the whole blood assays, the COX-2/COX-1 ratio for meloxicam was 0.2 compared to 0.9 for indomethacin confirming meloxicam's COX-2 selectivity. Conclusion: The results with human mucosa pieces would suggest that the better gastric tolerability of meloxican compared to indomethacin is related to its relatively lower inhibition of gastric mucosal PGE synthesis by COX-1.


PMID: 10848664

DOI: 10.1046/j.1365-2036.2000.00760.x

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