Rebamipide using in gastroesophageal reflux disease treatment

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Rebamipide is a mucoprotective drug which was developed in Japan in 1990. The therapeutic effect of rebamipide based on the induction of cyclooxygenase-2 and increasing level of prostaglandins, inhibition of oxygen free radicals production, epidermal growth factor stimulation, vascular endothelial growth factor, nitric oxide, and decreasing of lipid peroxidation and neutrophils migration. The combination of proton pump inhibitors and rebamipide is more effective in relieving of gastroesophageal reflux disease symptoms and reducing recurrence rate of disease. Using rebamipide in the treatment of gastroesophageal reflux disease is justified because this drug has a unique mechanism of action, which eliminating the main stages of pathogenesis of the disease.

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V. T. Ivashkin

Sechenov First Moscow State Medical University (Sechenov University)

ORCID iD: 0000-0002-6815-6015

Russian Federation, Moscow

акад. РАН, д.м.н., проф., зав. каф. пропедевтики внутренних болезней, гастроэнтерологии, гепатологии

A. S. Trukhmanov

Sechenov First Moscow State Medical University (Sechenov University)

ORCID iD: 0000-0003-3362-2968

Russian Federation, Moscow

д.м.н., проф. каф. пропедевтики внутренних болезней, гастроэнтерологии, гепатологии

M. I. Gonik

Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
ORCID iD: 0000-0002-0605-8057

Russian Federation, Moscow

клинический ординатор каф. пропедевтики внутренних болезней, гастроэнтерологии, гепатологии


  1. Ивашкин В.Т., Маев И.В., Трухманов А.С. и др. Клинические рекомендации Российской гастроэнтерологической ассоциации по диагностике и лечению гастроэзофагеальной рефлюксной болезни. Рос. журн. гастроэнтерологии, гепатологии, колопроктологии. 2017;27(4):75-95 [Ivashkin VT, Mayev IV, Trukhmanov AS, et al. Diagnostics and treatment of gastroesophageal reflux disease: clinical guidelines of the Russian gastroenterological association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2017;27(4):75-95 (In Russ.)]. doi: 10.22416/1382-4376-2017-27-4-75-95
  2. Hunt R, Armstrong D, Katelaris P, et al. World gastroenterology organisation global guidelines: GERD global perspective on gastroesophageal reflux disease. J Clin Gastroenterol. 2017;51(6):467-78. doi: 10.1097/MCG.0000000000000854
  3. Farré R. Pathophysiology of gastro-esophageal reflux disease: a role for mucosa integrity? Neurogastroenterol Motil. 2013;25(10):783-99. doi: 10.1111/nmo.12201
  4. Naito Y, Yoshida N, Yoshikawa T. Esophageal inflammation in gastroesophageal reflux disease (GERD): role of chemokines. Inflam Regeneration. 2006;5(26):428-36. doi: 10.2492/inflammregen.26.428
  5. Takeji Y, Urashima H, Aoki A, Shinohara H. Rebamipide Increases the Mucin-Like Glycoprotein Production in Corneal Epithelial Cells. J Ocular Pharmacol Ther. 2012;3(28):259-63. doi: 10.1089/jop.2011.0142
  6. Arakawa T, Higuchi K, Fujiwara Y, et al. 15th Anniversary of Rebamipide: Looking Ahead to the New Mechanisms and New Applications. Digestive Dis Sci. 2005;S1(50):S3-S11. doi: 10.1007/s10620-005-2800-9
  7. Yandrapu H, Marcinkiewicz M, Sarosiek I, et al. Role of Saliva in Esophageal Defense: Implications in Patients With Nonerosive Reflux Disease. Am J Med Sci. 2015;5(349):385-91. doi: 10.1097/MAJ.0000000000000443
  8. Yoshida N. Oxidative stress in digestive disease guest editor: yuji naito inflammation and oxidative stress in gastroesophageal reflux disease. J Clin Biochem Nutrition. 2007;40(1):13-23. doi: 10.3164/jcbn.40.13
  9. Евсютина Ю.В. и др. Системный иммунный ответ у пациентов с гастроэзофагеальной рефлюксной болезнью. Рос. журн. гастроэнтерологии, гепатологии, колопроктологии. 2015;25(5):32-8 [Yevsyutina YuV, Trukhmanov AS. The role of esophageal and stomach motility disorders in pathogenesis of gastroesophageal reflux disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2015;25(5):32-8 (In Russ.)].
  10. Goyal RK. Deleterious effects of prostaglandins on esophageal mucosa. Gastroenterology. 1980;5(78):1085-7.
  11. Takeuchi K, Nagahama K. Animal model of acid-reflux esophagitis: pathogenic roles of acid/pepsin, prostaglandins, and amino acids. BioMed Res Int. 2014. doi: 10.1155/2014/532594
  12. Goyal RK, Rattan S, Hersh T. Comparison of the Effects of Prostaglandins E1, E2, and A2, and of Hypovolumic Hypotension on the Lower Esophageal Sphincter. Gastroenterology. 1973;4(65):608-12.
  13. Jiménez P, Piazuelo E, Sánchez MT, et al. Free radicals and antioxidant systems in reflux esophagitis and Barrett’s esophagus. World J Gastroenterol. 2005;11(18):2697. doi: 10.3748/wjg.v11.i18.26
  14. Oh T-Y, Lee JS, Ahn BO, et al. Oxidative damages are critical in pathogenesis of reflux esophagitis: implication of antioxidants in its treatment. Free Radical Biol Med. 2001;8(30):905-15. doi: 10.1016/S0891-5849(01)00472-5
  15. Song JH, Han YM, Kim WH, et al. Oxidative stress from reflux esophagitis to esophageal cancer: the alleviation with antioxidants. Free Radical Res. 2016;10(50):1071-9. doi: 10.1080/10715762.2016.1181262
  16. Cheng L, Cao W, Behar J, et al. Inflammation induced changes in arachidonic acid metabolism in cat LES circular muscle. Am J Physiol Gastrointestinal Liver Physiol. 2005;4(288):G787-G797.
  17. PubChem Rebamipide.
  18. Kleine A, Kluge S, Peskar BM. Stimulation of prostaglandin biosynthesis mediates gastroprotective effect of rebamipide in rats. Digestive Dis Sci. 1993;8(38):1441-9. doi: 10.1007/BF01308601
  19. Sun W-H, Tsuji S, Tsujii M, et al. Induction of cyclooxygenase-2 in rat gastric mucosa by rebamipide, a mucoprotective agent. J Pharmacol Experim Ther. 2000;2(295):447-52.
  20. Katada K, Yoshida N, Isozaki Y, et al. Prevention by Rebamipide of Acute Reflux Esophagitis in Rats. Digestive Dis Sci. 2005;S1(50):S97-S103. doi: 10.1007/s10620-005-2813-4
  21. Gweon T-G, Park JH, Kim BW, et al. Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease. Gut Liver. 2018;1(12):46-50. doi: 10.5009/gnl17078
  22. Kohata Y, Nakahara K, Tanigawa T, et al. Rebamipide Alters the Esophageal Microbiome and Reduces the Incidence of Barrett’s Esophagus in a Rat Model. Digestive Dis Sci. 2015;9(60):2654-61. doi: 10.1007/s10620-015-3662-4
  23. Kauppila JH, Selander KS. Toll-like receptors in esophageal cancer. Frontiers Immunol. 2014;5:200.
  24. Hong SJ, Park SH, Moon JS, et al. The Benefits of Combination Therapy with Esomeprazole and Rebamipide in Symptom Improvement in Reflux Esophagitis: An International Multicenter Study. Gut Liver. 2016;6(10):910-6.
  25. Yoshida N, Kamada K, Tomatsuri N, et al. Management of Recurrence of Symptoms of Gastroesophageal Reflux Disease: Synergistic Effect of Rebamipide with 15 mg Lansoprazole. Digestive Dis Sci. 2010;12(55):3393-8. doi: 10.1007/s10620-010-1166-9
  26. Andreev DN, Maev IV, Dicheva DT. Efficiency of the Inclusion of Rebamipide in the Eradication Therapy for Helicobacter pylori Infection: Meta-Analysis of Randomized Controlled Studies. J Clin Med. 2019;8(9). pii: E1498. doi: 10.3390/jcm8091498
  27. Андреев Д.Н., Дичева Д.Т., Маев И.В. Возможности оптимизации эрадикационной терапии инфекции Helicobacter pylori в современной клинической практике. Терапевтический архив. 2017;89(2):84-90 [Andreev DN, Dicheva DT, Maev IV. Possibilities for optimization of eradication therapy for Helicobacter pylori infection in modern clinical practice. Therapeutic Archive. 2017;89(2):84-90 (In Russ.)]. doi: 10.17116/terarkh201789284-90
  28. Андреев Д.Н., Маев И.В., Дичева Д.Т. и др. Эффективность и безопасность применения ребамипида в схеме тройной эрадикационной терапии инфекции Helicobacter pylori: проспективное рандомизированное сравнительное исследование. Терапевтический архив. 2018;90(8):27-32. [Andreev DN, Maev IV, Dicheva DT, et al. Efficacy and safety of the use of rebamipide in the scheme of triple eradication therapy of Helicobacter pylori infection: a prospective randomized comparative study. Therapeutic Archive. 2018;90(8):27-32 (In Russ.)]. doi: 10.26442/terarkh201890827-32
  29. Dicheva D, Andreev D, Maev I. Efficacy and safety of including rebamipide in the triple eradication therapy of Helicobacter pylori infection. Helicobacter. 2018;23(S1):43. doi: 10.1111/hel.12525
  30. Terano A, Arakawa T, Sugiyama T, et al; Rebamipide Clinical Study Group. Rebamipide, a gastro-protective and anti-inflammatory drug, promotes gastric ulcer healing following eradication therapy for Helicobacter pylori in a Japanese population: a randomized, double-blind, placebo-controlled trial. J Gastroenterol. 2007;42(8):690-3.
  31. Zhang S, Qing Q, Bai Y, et al. Rebamipide helps defend against nonsteroidal anti-inflammatory drugs induced gastroenteropathy: a systematic review and meta-analysis. Dig Dis Sci. 2013;58(7):1991-2000. doi: 10.1007/s10620-013-2606-0

Supplementary files

Supplementary Files Action
Fig. 1. Levels of cytoprotection of the esophagus [8].

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Fig. 2. Features of intercellular compounds in different types of epithelium [3].

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Fig. 3. Correlation of IL-8 expression and the degree of esophagitis in GERD [4].

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Fig. 4. Dependence of the reduction of NPS pressure on the GHG dose in possums [12].

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Fig. 5. Scheme of the pathological process of acid-dependent diseases of the esophagus with the participation of oxygen free radicals [8].

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Fig. 6. Change in the level of expression of tight contact proteins during modeling of GERD in rats [21].

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Fig. 7. Change in the expression level of microbiota in rats in the rebamipid and control group [22].

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Fig. 8. Change in the symptoms of reflux esophagitis in 501 patients in the monotherapy group with esomeprazole and in the combination group of rebamipid and esomeprazole [24].

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