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Determinants of the short-term gastric damage caused by NSAIDs in man Bjarnason I; Scarpignato C; Takeuchi K; Rainsford KDAliment Pharmacol Ther 2007[Jul]; 26 (1): 95-106BACKGROUND: The short-term gastric damage seen with non-steroidal anti-inflammatory drugs (NSAIDs) in man may involve inhibition of cyclooxygenase (COX-1) and COX-2 as well as the topical irritancy, which is dependant on the acidity (pKa) and/or lipophilicity (log P(7.4)). AIM: To study the quantitative relationship between NSAID-induced short-term gastric damage, their physicochemical properties and contrasting roles of COX-1 and COX-2 inhibition. METHODS: We identified studies that allowed a qualitative comparison of the gastric injury (Lanza scores) induced by NSAIDs with their pKa and log P(7.4). Damage was correlated with gastric COX inhibition and potency to inhibit COX-1 and 2 and their COX-2/COX-1 selectivity ratio. RESULTS: The gastric damage correlates significantly with pKa (r = -0.69; P < 0.01), log P (r = -0.58, P < 0.05) and potency of the NSAIDs to inhibit COX-1 (r = -0.61, P < 0.02), but not with COX-2 inhibition or COX-2/COX-1 selectivity. CONCLUSION: Against a background of COX-1 and COX-2 inhibition, the physicochemical properties of NSAID appear to play an important role in short-term gastric damage.|Anti-Inflammatory Agents, Non-Steroidal/*adverse effects[MESH]|Cyclooxygenase Inhibitors/*adverse effects[MESH]|Gastrointestinal Diseases/*chemically induced[MESH]|Humans[MESH] |
