alexa In vitro and in vivo protection against indomethacin-induced small intestinal injury by proton pump inhibitors, acid pump antagonists, or indomethacin-phosphatidylcholine.
Pharmaceutical Sciences

Pharmaceutical Sciences

Pharmaceutica Analytica Acta

Author(s): Lim YJ, Phan TM, Dial EJ, Graham DY, Lichtenberger LM

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Abstract BACKGROUND/AIMS: Proton pump inhibitors (PPIs) are widely used to prevent nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcers. NSAIDs produce small intestinal injury and some PPIs have been reported to protect against NSAID-induced small bowel injury in rats. The aim of this study was to compare PPIs, revaprazan, and phosphatidylcholine-associated indomethacin (Indo-PC) for protection against indomethacin (Indo)-induced small bowel injury. METHODS: Rat intestinal epithelial cells (IEC-6) were pretreated with omeprazole, lansoprazole, or revaprazan prior to exposure to Indo or Indo-PC. Cell viability was assessed by methyl thiazolyl tetrazolium assay. Omeprazole, lansoprazole, or revaprazan was administered orally to rats prior to the vehicle or Indo. Indo-PC was administered alone. After 24 h, small intestinal erosions were counted; intestinal bleeding was assessed as the hemoglobin concentration of small intestinal fluid. RESULTS: Omeprazole, lansoprazole, and revaprazan did not protect against Indo-induced IEC-6 cell injury. Indo-PC was less damaging in vitro than Indo alone. In vivo, neither omeprazole nor lansoprazole protected against Indo-induced small bowel injury; however, revaprazan pretreatment and Indo-PC resulted in significantly fewer erosions (>50\% reduction) or bleeding (>80\% reduction). CONCLUSION: PPIs showed no small bowel protective effect in vitro or in vivo. Revaprazan showed a small bowel protective effect in vivo, whereas Indo-PC was protective both in vitro and in vivo. Copyright © 2012 S. Karger AG, Basel.
This article was published in Digestion and referenced in Pharmaceutica Analytica Acta

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