Experimental evidence of the benefit of misoprostol beyond the stomach in humans.
Nonsteroidal antiinflammatory drugs (NSAID) cause inflammation of the small intestine in 60 to 70% of patients receiving these drugs for more than 6 months. The importance of the inflammation lies in the associated complications of blood and protein loss and in the occasional development of unique small intestinal strictures requiring surgery. The pathogenesis of the inflammation is unknown. However, increased intestinal mucosal permeability due to NSAID appears to be a prerequisite; increased permeability allows exposure of the mucosa to lumenal toxins, which results in neutrophil chemotaxis and, hence, inflammation. In a study assessing the possible protective effect of misoprostol on indomethacin-induced increased small intestinal permeability, 12 volunteers underwent combined absorption/permeability tests prior to and following administration of misoprostol and/or indomethacin. Indomethacin increased intestinal permeability significantly as assessed by 51Cr-EDTA/L-rhamnose urine excretion ratio, and concomitant administration of misoprostol produced a significant protective effect. These results conform to the suggestion that NSAID-induced changes in intestinal permeability may be due to an imbalance between mucosal prostaglandins and leukotrienes. Longterm studies of the coadministration of misoprostol with NSAID are indicated to assess whether this agent reduces the severity of NSAID enteropathy.
Bjarnason
I
I
Section of Gastroenterology, Clinical Research Centre, Harrow, Middlesex, UK.
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D004751:Enteritis / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D016595:Misoprostol; D010003:Osteoarthritis / Q000188:drug therapy
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D016595:Misoprostol; D000527:Alprostadil