The gastrointestinal system Alterations in gastrointestinal (GI) function are common side effects of many drugs, not limited to those administered orally [1,2]. Changes in bowel habits (constipation or diarrhea) and gastric mucosal irritation are the most common side effects that are covered at least in part by classical technical approach involving the evaluation of gastric emptying, intestinal and colonic transit, as well as direct gastric mucosal damage score evaluation [3,4]. For example, increased small intestinal permeability caused by nonsteroidal anti-inŸammatory drugs (NSAIDs) is probably a prerequisite for NSAID enteropathy, a source of morbidity in patients with rheumatoid arthritis. These results were supported by the 51Cr EDTA/Lrhamnose urine excretion ratios, which reŸect changes in intestinal permeability [5]. Effects of drugs on intestinal tone has appeared recently to be of importance since compounds having a relaxatory effect on colonic muscular tone may favor the occurrence of ischemia. However, there is now evidence that other functions of the gut may be affected, giving rise to more chronic alteration and/or reactivity to oral pathogen or irritant or alteration in digestion and presence of gut hypersensitivity to mechanical stimuli. Several other gut functions such as epithelial barrier regulating both transcellular and paracellular absorption may be altered as well as enzymes, hormones, and ion secretion. Intestinal and colonic microŸora may be also affected by orally administered drugs. Viscerosensitivity of the gut is affected by the immune status of the mucosa. There is accumulated evidence that orally administered drugs may modify this immune status giving rise to sensitization of sensory nerve terminals, but a direct action after epithelial absorption on receptors located on terminals of primary afferent neurons is possible. These effects may trigger abdominal pain.