The evaluation of acute gastrointestinal toxicity of NSAIDs in phase I clinical trials: a critical appraisal

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs and, excluding salicylates, are represented by more than 100 different compounds. Mucosal damage to the upper gastrointestinal (GI) tract is a side-effect common to all NSAIDs. Despite their obvious benefits, the damage they cause in the GI tract is a major health problem in current clinical practice [1]. Although a vast amount of information has accumulated on this topic over many years, only the data published in the very recent past provide convincing evidence that NSAIDs cause severe GI complication and allow the risk to be roughly quantified. Upper GI toxicity occuring after administration of NSAIDs can present a wide spectrum of clinical expressions ranging from relatively mild, but nonetheless discomforting, conditions such as epigastric pain and dyspepsia, to the more serious and potentially life-threatening states, namely GI ulceration and GI bleeding or perforation. Endoscopic evaluation of the upper GI tract in patients treated with NSAIDs reveals a number of lesions that range from simple erythema through diffuse erosions and/or microbleeding to ulceration [2–4]. Roth and Bennett [5] have recently proposed the term ‘NSAID gastropathy’ to describe those lesions associated with the upper GI tract toxicity that are encountered during NSAID therapy. Damage to the upper GI tract is not limited to the stomach, but can also involve the duodenum and, albeit infrequently, the oesophagus and the intestine.