Determinants of the short‐term gastric damage caused by NSAIDs in man

Summary Background 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.