Skip to main content

Advertisement

SpringerLink
Log in

Efficacy of rebamipide for diclofenac-induced small-intestinal mucosal injuries in healthy subjects: a prospective, randomized, double-blinded, placebo-controlled, cross-over study

  • Alimmentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Although obscure gastrointestinal bleeding cannot be detected by colonoscopy or upper endoscopy, wireless video capsule endoscopy (VCE) is capable of imaging it. Few data are available on medical therapy for patients with nonsteroidal anti-inflammatory drug (NSAID)-induced small-intestinal mucosal injuries. The aim of this study was to compare prevention by rebamipide and placebo of NSAID-induced smallintestinal injury in healthy subjects.

Methods

Ten healthy subjects who provided written informed consent were enrolled. Rebamipide or placebo plus diclofenac was administered with omeprazole for 7 days, and for an additional 7-day period with treatments reversed in the same subjects, with a 4-week washout period between treatments. VCE of the small intestine was performed four times, before and after each of the two study periods.

Results

The number of subjects with small-intestinal mucosal injuries was higher in the placebo group (8/10) than in the rebamipide group (2/10) (P = 0.023). Two cases of ulcer and one of bleeding were observed in the placebo group, while no ulcer or bleeding was observed in the rebamipide group.

Conclusions

Rebamipide had significantly higher efficacy than placebo in preventing NSAID-induced small-intestinal mucosal injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Zuckerman GR, Prakash C, Askin MP, Lewis BS. Lewis BS. AGA technical review on the evaluation and management of occult and obscure gastrointestinal bleeding. Gastroenterology 2000;118:201–221.

    Article  PubMed  CAS  Google Scholar 

  2. MacKenzie JF. Push enteroscopy. Gastrointest Endosc Clin North Am 1999;1:29–36.

    Google Scholar 

  3. Seensalu R. The sonde examination. Gastrointest Endosc Clin North Am 1999;1:37–59.

    Google Scholar 

  4. Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature 2000;405:417.

    Article  PubMed  CAS  Google Scholar 

  5. Gong F, Swain P, Mills T. Wireless endoscopy. Gastrointest Endosc 2000;51:725–729.

    Article  PubMed  CAS  Google Scholar 

  6. Graham DY, Opekun AR, Willingham FF, Qureshi WA. Visible small-intestinal mucosal injury in chronic NSAID users. Clin Gastroenterol Hepatol 2005;3:55–59.

    Article  PubMed  Google Scholar 

  7. Goldstein JL, Eisen GM, Lewis B, Gralnek IM, Zlotnick S, Fort JG. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clin Gastroenterol Hepatol 2005;3:133–141.

    Article  PubMed  Google Scholar 

  8. Sigthorsson G, Simpson RJ, Walley M, Anthony A, Foster R, Hotz-Behoftsitz C, et al. COX-1 and 2, intestinal integrity and pathogenesis of NSAID-enteropathy in mice. Gastroenterology 2002;122:1913–1923.

    Article  PubMed  CAS  Google Scholar 

  9. Whittle BJR. Mechanisms underlying intestinal injury induced by anti-inflammatory COX inhibitors. Eur J Pharmacol 2004;500:427–439.

    Article  PubMed  CAS  Google Scholar 

  10. Bjarnason I, Williams P, So A, Zanelli GD, Levi AJ, Gumpel JM, et al. Intestinal permeability and inflammation in rheumatoid arthritis; effects of non-steroidal anti-inflammatory drugs. Lancet 1984;ii:1171–1174.

    Article  Google Scholar 

  11. Bjarnason I, Smethurst P, Fenn CG, Lee CE, Menzies IS, Levi AJ. Misoprostol reduces indomethacin induced changes in human small intestinal permeability. Dig Dis Sci 1989;34:407–411.

    Article  PubMed  CAS  Google Scholar 

  12. Bjarnason I, Hayllar J, Smethurst P, Price A, Gumpel MJ. Metronidazole reduces inflammation and blood loss in NSAID enteropathy. Gut 1992;33:1204–1208.

    Article  PubMed  CAS  Google Scholar 

  13. Hayllar J, Smith T, Macpherson A, Price AB, Gumpel M, Bjarnason I. Nonsteroidal anti-inflammatory drug induced small intestinal inflammation and blood loss: effect of sulphasalazine and other disease modifying drugs. Arthritis Rheum 1994;37:1146–1150.

    Article  PubMed  CAS  Google Scholar 

  14. Yamasaki K. Effect of OPC-12759, a novel antiulcer agent, on chronic and acute experimental gastric ulcer, and gastric secretion in rats. Jpn J Pharmacol 1989;49:441–448.

    Article  PubMed  CAS  Google Scholar 

  15. Arakawa T. Rebamipide, a novel prostaglandin-inducer, accelerates healing and reduces relapse of acetic acid-induced rat gastric ulcer: comparison with cimetidine. Dig Dis Sci 1995;40:2469–2472.

    Article  PubMed  CAS  Google Scholar 

  16. Mizoguchi H, Ogawa Y, Kanatsu K, Tanaka A, Kato S, Takeuchi K. Protective effect of rebamipide on indomethacin-induced intestinal damage in rats. J Gastroenterol Hepatol 2001;16:1112–1119.

    Article  PubMed  CAS  Google Scholar 

  17. Naito Y, Yoshikawa T, Tanigawa T, Sakurai K, Yamasaki K, Uchida M, et al. Hydroxyl radical scavenging by rebamipide and related compounds: electron paramagnetic resonance study. Free Radic Biol Med 1995;18:117–123.

    Article  PubMed  CAS  Google Scholar 

  18. Laharie D, Ménard S, Asencio C, Vidal-Martinez T, Rullier A, Zerbib F, et al. Effect of rebamipide on the colonic barrier in interleukin-10-deficient mice. Dig Dis Sci 2007;52:84–92.

    Article  PubMed  CAS  Google Scholar 

  19. Zea-Iriarte WL, Makiyama K, Goto S, Murase K, Urata Y, Sekine I, et al. Impairment of antioxidants in colonic epithelial cells isolated from trinitrobenzene Sulphonic acid-induced colitis rats. Scand J Gastroenterol 1996;31:985–992.

    Article  PubMed  CAS  Google Scholar 

  20. Niwa Y, Nakamura M, Ohmiya N, Itoh A, Hirooka Y, Goto H. Ileal cancer and erosions in the small intestine revealed by capsule endoscopy. Endoscopy 2007: Feb 7 [Epub ahead of print].

  21. Sidhu R, Sanders DS, McAlindon ME, Kapur K. Capsule endoscopy for the evaluation of nonsteroidal anti-inflammatory drug-induced enteropathy: United Kingdom pilot data. Gastrointest Endosc 2006;64:1035.

    Article  PubMed  Google Scholar 

  22. Maiden L, Thjodleifsson B, Seigal A, Bjarnason II, Scott D, Birgisson S, et al. Long-term effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 selective agents on the small bowel: a cross-sectional capsule enteroscopy study. Clin Gastroenterol Hepatol 2007;5:1040–1045.

    Article  PubMed  Google Scholar 

  23. Naito Y, Yoshikawa T, Iinuma S, Yagi N, Matsuyama K, Boku Y, et al. Rebamipide protects against indomethacin-induced gastric mucosal injury in healthy volunteers in a double-blind, placebocontrolled study. Dig Dis Sci 1998;43:83–89S.

    Google Scholar 

  24. Park S-H, Cho C-S, Lee O-Y, Jun J-B, Lin S-R, Zhou L-Y, et al. Comparison of prevention of NSAID-induced gastrointestinal complications by rebamipide and misoprostol: a randomized, multicenter, controlled trial-STORM study. J Clin Biochem Nutr 2007;40:148–155.

    Article  PubMed  CAS  Google Scholar 

  25. Yamao J, Kikuchi E, Matsumoto M, Nakayama M, Ann T, Kojima H, et al. Assessing the efficacy of famotidine and rebamipide in the treatment of gastric mucosal lesions in patients receiving long-term NSAID therapy (FORCE—famotidine or rebamipide in comparison by endoscopy). J Gastroenterol 2006;41:1178–1185.

    Article  PubMed  CAS  Google Scholar 

  26. Furuta R, Ando T, Watanabe O, Maeda O, Ishiguro K, Ina K, et al. Rebamipide enema therapy as a treatment for patients with active distal ulcerative colitis. J Gastroenterol Hepatol 2007;22:261–267.

    Article  PubMed  CAS  Google Scholar 

  27. Bjarnason I, Smethurst P, Fenn CG, Lee CE, Menzies IS, Levi AJ. Misoprostol reduces indomethacin-induced changes in human small intestinal permeability. Dig Dis Sci 1989;34:407–411.

    Article  PubMed  CAS  Google Scholar 

  28. Davies GR, Wilkie ME, Rampton DS. Effects of metronidazole and misoprostol on indomethacin-induced changes in intestinal permeability. Dig Dis Sci 1993;38:417–425.

    Article  PubMed  CAS  Google Scholar 

  29. Kuroda M, Yoshida N, Ichikawa H, Takagi T, Okuda T, Naito Y, et al. Lansoprazole, a proton pump inhibitor, reduces the severity of indomethacin-induced rat enteritis. Int J Mol Med 2006;17:89–93.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Yasumasa Niwa, Masanao Nakamura, Naoki Ohmiya, Osamu Maeda, Takafumi Ando, Akihiro Itoh, Yoshiki Hirooka & Hidemi Goto

Authors
  1. Yasumasa Niwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masanao Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naoki Ohmiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Osamu Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takafumi Ando
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akihiro Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoshiki Hirooka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hidemi Goto
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Niwa, Y., Nakamura, M., Ohmiya, N. et al. Efficacy of rebamipide for diclofenac-induced small-intestinal mucosal injuries in healthy subjects: a prospective, randomized, double-blinded, placebo-controlled, cross-over study. J Gastroenterol 43, 270–276 (2008). https://doi.org/10.1007/s00535-007-2155-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-007-2155-4

Key words

Search

Navigation