title: Determinants of the short-term gastric damage caused by NSAIDs in man.
abstract: 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)).
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Guy's, King's, St Thomas' Medical School, London, UK. ingvar.bjarnason@kcl.ac.uk
authors.forename: I
authors.initials: I
authors.lastname: Bjarnason
authors.forename: C
authors.initials: C
authors.lastname: Scarpignato
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: K D
authors.initials: KD
authors.lastname: Rainsford
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors