References

mrj

Современная ревматология

Modern Rheumatology Journal

1996-70122310-158X

IMA-PRESS, LLC

10.14412/1996-7012-2016-4-97-105

mrj-726

Research Article

ОБЗОРЫ

REVIEWS

РЕБАМИПИД: ЭФФЕКТИВНАЯ МЕДИКАМЕНТОЗНАЯ ПРОФИЛАКТИКА НПВП-ЭНТЕРОПАТИИ ВОЗМОЖНА

REBAMIPIDE: EFFECTIVE DRUG PREVENTION OF NSAID ENTEROPATHY IS POSSIBLE

Мороз

Е. В.

Moroz

E. V.

Каратеев

А. Е.

Karateev

A. E.

Контакты: Андрей Евгеньевич Каратеев; ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», 115522, Москва, Каширское шоссе, 34А

Contact: Andrei Evgenyevich Karateev; V.A. Nasonova Research Institute of Rheumatology, 34A, Kashirskoe Shosse, Moscow 115522

aekarat@yandex.ru

Главный военный клинический госпиталь имени акад. Н.Н. БурденкоРоссияAcad. N.N. Burdenko Main Military Clinical HospitalRussian Federation

Научно-исследовательский институт ревматологии им. В.А. НасоновойРоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation

2016

16122016

10497105

2016

Мороз Е.В., Каратеев А.Е.

Moroz E.V., Karateev A.E.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://mrj.ima-press.net/mrj/article/view/726

Предупреждение развития осложнений со стороны желудочно-кишечного тракта (ЖКТ) – важнейший элемент рационального применения нестероидных противовоспалительных препаратов (НПВП) и низких доз аспирина (НДА). Долгое время единственным средством медикаментозной профилактики этих осложнений были ингибиторы протонной помпы (ИПП). Однако ИПП эффективны лишь для профилактики и лечения патологии верхних отделов ЖКТ (НПВП-гастропатия), но не патологии тонкой кишки (НПВП-энтеропатия). Сегодня у российских врачей появился новый инструмент защиты слизистой оболочки ЖКТ – ребамипид1 . Действие этого препарата отлично от такового ИПП: он является типичным гастрои энтеропротектором, усиливающим синтез эндогенных простагландинов и обладающим значимым противовоспалительным потенциалом. Препарат давно и широко используется врачами Японии, Южной Кореи и Китая как эффективное и безопасное средство для лечения многих заболеваний пищеварительной системы. Имеется серьезная доказательная база, подтверждающая эффективность ребамипида для профилактики и лечения НПВП-гастропатии и НПВП-энтеропатии (в том числе патологии, вызванной приемом НДА). По данным контролируемых исследований, он не уступает «классическому» гастропротектору мизопростолу, существенно превосходя последний по переносимости. В настоящем обзоре представлен механизм действия ребамипида, приведены основные клинические исследования, в которых изучалось его терапевтическое действие при НПВП-гастропатии и НПВП-энтеропатии.

Prevention of gastrointestinal tract (GIT) complications is the most important element for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin (LDA). Proton pump inhibitors (PPIs) have long been the only medication to prevent these complications. However, PPIs are only effective in preventing and treating upper GIT diseases (NSAID gastropathy) rather than small intestinal injury (NSAID enteropathy). Rebamipide has emerged as a novel agent to protect the gastrointestinal mucosa today. The effect of the drug differs from that of PPIs: it is a typical gastroand enteroprotector that enhances the synthesis of endogenous prostaglandins and possesses a significant anti-inflammatory potential. Rebamipide has long been widely used by doctors inJapan,South Korea, andChinaas an effective and safe agent for the treatment of many diseases of the digestive system. There is a strong evidence base for the efficacy of rebamipide in preventing and treating NSAID gastropathy and NSAID enteropathy (including LDA-induced injuries). Controlled studies have found that the drug is not inferior to the classic gastroprotective agent misoprostol, significantly outperforming the latter in its tolerability. This review describes the mechanism of action of rebamipide and main clinical trials of its therapeutic effect in NSAID gastropathy and NSAID enteropathy.

нестероидные противовоспалительные препаратынизкие дозы аспиринаНПВП-гастропатияНПВП-энтеропатияингибиторы протонной помпымизопростолребамипид

nonsteroidal anti-inflammatory drugslow-dose aspirinNSAID gastropathyNSAID enteropathyproton pump inhibitorsmisoprostolrebamipide

References1

Morrissey MB, Herr K, Levine C. Public health imperative of the 21st century: innovations in palliative care systems, services, and supports to improve health and well-being of older americans. Gerontologist. 2015 Apr;55(2):245-51. doi:10.1093/geront/gnu178. Epub 2015 Feb 17.

Каратеев АЕ, Насонов ЕЛ, Яхно НН и др. Клинические рекомендации «Рациональное применение нестероидных противовоспалительных препаратов (НПВП) в клинической практике». Современная ревматология. 2015;9(1):4-24. [Karateev AE, Nasonov EL, Yakhno NN, et al. Clinical guidelines «Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice». Sovremennaya revmatologiya = Modern Rheumatology Journal. 2015;9(1):4-24. (In Russ.)]. 3. Brune K, Patrignani P. New insights into the use of currently available non-steroidal anti-inflammatory drugs. J Pain Res. 2015 Feb 20;8:105-18. doi: 10.2147/JPR.S75160. eCollection 2015.

Murray CJ, Barber RM, Foreman KJ, et al. Global, regional, and national disabilityadjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition. Lancet. 2015 Nov 28;386(10009):2145-91. doi:10.1016/S0140-6736(15)61340-X. Epub 2015 Aug 28.

Wilson N, Sanchez-Riera L, Morros R, et al. Drug utilization in patients with OA: a population-based study. Rheumatology (Oxford). 2015 May;54(5):860-7. doi:10.1093/rheumatology/keu403. Epub 2014 Oct 21.

Breivik H, Collett B, Ventafridda V, et al. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006 May;10(4):287-333. Epub 2005 Aug 10.

Langley P. The prevalence, correlates and treatment of pain in the European Union. Curr Med Res Opin. 2011 Feb;27(2):463-80. doi: 10.1185/03007995.2010.542136. Epub 2011 Jan 11.

Zhou Y, Boudreau DM, Freedman AN. Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population. Pharmacoepidemiol Drug Saf. 2014;23(1):43–50.

Gu Q, Dillon CF, Eberhardt MS, et al. Preventive aspirin and other antiplatelet medication use among U.S. adults aged ≥40 years: data from the national health and nutrition examination survey, 2011-2012. Public Health Rep. 2015 NovDec;130(6):643-54.

Scarpignato C, Lanas A, Blandizzi C, et al. Safe prescribing of non-steroidal antiinflammatory drugs in patients with osteoarthritis – an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks. BMC Med. 2015 Mar 19;13:55. doi: 10.1186/s12916-015-0285-8.

Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci. 2013;16(5):821-47.

Tielleman T, Bujanda D, Cryer B. Epidemiology and risk factors for upper gastrointestinal bleeding. Gastrointest Endosc Clin N Am. 2015 Jul;25(3):415-28. doi:10.1016/j.giec.2015.02.010.

Sostres C, Gargallo CJ, Lanas A. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res Ther. 2013;15 Suppl 3:S3. doi:10.1186/ar4175. Epub 2013 Jul 24.

Hsu PI, Tsai TJ. Epidemiology of Upper Gastrointestinal Damage Associated with Low-Dose Aspirin. Curr Pharm Des. 2015;21(35):5049-55.

Scheiman JM, Devereaux PJ, Herlitz J, et al. Prevention of peptic ulcers with esomeprazole in patients at risk of ulcer development treated with low-dose acetylsalicylic acid: a randomised, controlled trial (OBERON). Heart. 2011 May;97(10): 797-802. doi:10.1136/hrt.2010.217547. Epub 2011 Mar 17.

Davies N, Saleh J, Skjodt N. Detection and prevention of NSAID-induced enteropathy. J Pharm Pharm Sci. 2000 Jan-Apr;3 (1):137-55.

Allison M, Howatson A, Torrance C, et al. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drags. N Engl J Med. 1992 Sep 10; 327(11):749-54.

Sands G, Shell B, Zhang R. Adverse events in patients with blood loss: a pooled analysis of 51 clinical studies from the celecoxib clinical trial database. Open Rheumatol J. 2012;6:44-9. doi:10.2174/1874312901206010044. Epub 2012 May 11.

Goldstein J, Eisen G, Lewis B, et al. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clin Gastroenterol Hepatol. 2005 Feb;3(2):133-41.

Goldstein J, Eisen G, Lewis B, et al. Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy. Aliment Pharmacol Ther. 2007 May 15;25(10):1211-22.

Hawkey CJ, Ell C, Simon B, et al. Less small-bowel injury with lumiracoxib compared with naproxen plus omeprazole. Clin Gastroenterol Hepatol. 2008;6(5):536-44. doi:10.1016/j.cgh.2007.12.023. Epub 2008 Jan 31.

Tacheci I, Bradna P, Douda T, et al. Small intestinal injury in NSAID users suffering from rheumatoid arthritis or osteoarthritis. Rheumatol Int. 2016 Aug 22. [Epub ahead of print]

Pavlidis P, Bjarnason I. Aspirin Induced Adverse Effects on the Small and Large Intestine. Curr Pharm Des. 2015;21(35): 5089-93.

Sostres C, Lanas A. Epidemiology of Low Dose Aspirin Damage in the Lower Gastrointestinal Tract. Curr Pharm Des. 2015;21(35):5094-100.

Shiotani A, Haruma K, Nishi R, et al. Randomized, double-blind, pilot study of geranylgeranylacetone versus placebo in patients taking low-dose enteric-coated aspirin. Low-dose aspirin-induced small bowel damage. Scand J Gastroenterol. 2010 Mar;45(3):292-8. doi:10.3109/00365520903453182.

Syer SD, Blackler RW, Martin R, et al. NSAID enteropathy and bacteria: a complicated relationship. J Gastroenterol. 2015 Apr;50(4):387-93. doi:10.1007/s00535-014-1032-1. Epub 2015 Jan 10.

Maiden L, Thjodleifsson B, Seigal A, et al. Long-term effects of nonsteroidal antiinflammatory drugs and cyclooxygenase-2 selective agents on the small bowel: a crosssectional capsule enteroscopy study. Clin Gastroenterol Hepatol. 2007 Sep;5(9):1040-5. Epub 2007 Jul 10.

Rostom A, Muir K, Dube C, et al. Prevention of NSAID-related upper gastrointestinal toxicity: a meta-analysis of traditional NSAIDs with gastroprotection and COX-2 inhibitors. Drug Healthc Patient Saf. 2009;1:47-71. Epub 2009 Oct 28.

Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995 Aug 15;123(4):241-9.

Fujimori S, Seo T, Gudis K, et al. Prevention of nonsteroidal anti-inflammatory drug-induced small-intestinal injury by prostaglandin: a pilot randomized controlled trial evaluated by capsule endoscopy. Gastrointest Endosc. 2009 Jun;69(7):1339-46. doi:10.1016/j.gie.2008.08.017. Epub 2009 Feb 24.

Watanabe T, Sugimori S, Kameda N, et al. Small bowel injury by low-dose entericcoated aspirin and treatment with misoprostol: a pilot study. Clin Gastroenterol Hepatol. 2008 Nov;6(11):1279-82. doi:10.1016/j.cgh.2008.06.021.

Raskin JB, White RH, Jackson JE, et al. Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens. Ann Intern Med. 1995;123:344-350. doi:10.7326/0003-4819-123-5-199509010-00004.

Marlicz W, Loniewski I, Grimes DS, Quigley EM. Nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and gastrointestinal injury: contrasting interactions in the stomach and small intestine. Mayo Clin Proc. 2014 Dec;89(12):1699-709. doi:10.1016/j.mayocp.2014.07.015. Epub 2014 Oct 29.

Clooney AG, Bernstein CN, Leslie WD, et al. A comparison of the gut microbiome between long-term users and non-users of proton pump inhibitors. Aliment Pharmacol Ther. 2016 May;43(9):974-84. doi:10.1111/apt.13568. Epub 2016 Feb 29.

Janarthanan S, Ditah I, Adler DG, Ehrinpreis MN. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol. 2012 Jul;107(7):1001-10. doi:10.1038/ajg.2012.179. Epub 2012 Jun 19.

Bavishi C, Dupont HL. Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection. Aliment Pharmacol Ther. 2011 Dec;34 (11-12):1269-81. doi:10.1111/j.1365-2036.2011.04874.x. Epub 2011 Oct 17.

Verhaegh BP, de Vries F, Masclee AA, et al. High risk of drug-induced microscopic colitis with concomitant use of NSAIDs and proton pump inhibitors. Aliment Pharmacol Ther. 2016 May;43(9):1004-13. doi:10.1111/apt.13583. Epub 2016 Mar 9.

Naito Y, Yoshikawa T. Rebamipide: a gastrointestinal protective drug with pleiotropic activities. Expert Rev Gastroenterol Hepatol. 2010 Jun;4(3):261-70. doi:10.1586/egh.10.25.

Arakawa T, Higuchi K, Fujiwara Y, et al. 15th anniversary of rebamipide: looking ahead to the new mechanisms and new applications. Dig Dis Sci. 2005 Oct;50 Suppl 1:S3-S11.

Matysiak-Budnik T, Heyman M, Megraud F. Review article: rebamipide and the digestive epithelial barrier. Aliment Pharmacol Ther. 2003 Jul;18 Suppl 1:55-62.

Haruma K, Ito M. Review article: clinical significance of mucosal-protective agents: acid, inflammation, carcinogenesis and rebamipide. Aliment Pharmacol Ther. 2003 Jul;18 Suppl 1:153-9.

Nagano Y, Matsui H, Muramatsu M, et al. Rebamipide significantly inhibits indomethacin-induced mitochondrial damage, lipid peroxidation, and apoptosis in gastric epithelial RGM-1 cells. Dig Dis Sci. 2005 Oct;50 Suppl 1:S76-83.

Tarnawski A, Arakawa T, Kobayashi K. Rebamipide treatment activates epidermal growth factor and its receptor expression in normal and ulcerated gastric mucosa in rats: one mechanism for its ulcer healing action? Dig Dis Sci. 1998 Sep;43(9 Suppl):90S-98S.

Ishihara T, Tanaka K, Tashiro S, et al. Protective effect of rebamipide against celecoxib-induced gastric mucosal cell apoptosis. Biochem Pharmacol. 2010 Jun 1;79(11): 1622-33. doi:10.1016/j.bcp.2010.01.030. Epub 2010 Feb 2.

Aihara M, Azuma A, Takizawa H, et al. Molecular analysis of suppression of interleukin-8 production by rebamipide in Helicobacter pylori – stimulated gastric cancer cell lines. Dig Dis Sci. 1998;43(9 Suppl): 174S–180S.

Hiratsuka T, Futagami S, Shindo T, et al. Rebamipide reduces indomethacin-induced gastric injury in mice via down-regulation of ICAM-1 expression. Dig Dis Sci. 2005 Oct;50 Suppl 1:S84-9.

Tanigawa T, Watanabe T, Otani K, et al. Rebamipide inhibits indomethacin-induced small intestinal injury: possible involvement of intestinal microbiota modulation by upregulation of ?-defensin 5. Eur J Pharmacol. 2013 Mar 15;704(1-3):64-9. doi:10.1016/j.ejphar.2013.02.010. Epub 2013 Feb 18.

Zhang S, Qing Q, Bai Y, et al. Rebamipide helps defend against nonsteroidal anti-inflammatory drugs induced gastroenteropathy: a systematic review and metaanalysis. Dig Dis Sci. 2013 Jul;58(7): 1991-2000. doi:10.1007/s10620-013-2606-0. Epub 2013 Feb 28.

Hasegawa M, Horiki N, Tanaka K, et al. The efficacy of rebamipide add-on therapy in arthritic patients with COX-2 selective inhibitor-related gastrointestinal events: a prospective, randomized, open-label blinded-endpoint pilot study by the GLORIA study group. Mod Rheumatol. 2013 Nov;23(6):1172-8. doi:10.1007/s10165-012-0819-2. Epub 2013 Jan 10.

Park SH, Cho CS, Lee OY, et al. Comparison of prevention of NSAIDinduced gastrointestinal complications by rebamipide and misoprostol: a randomized, multicenter, controlled trial-STORM STUDY. J Clin Biochem Nutr. 2007 Mar;40(2):148-55. doi:10.3164/jcbn.40.148.

Kim JH, Park SH, Cho CS, et al. Preventive efficacy and safety of rebamipide in nonsteroidal anti-inflammatory druginduced mucosal toxicity. Gut Liver. 2014 Jul;8(4):371-9. doi:10.5009/gnl.2014.8.4.371. Epub 2013 Dec 24.

Niwa Y, Nakamura M, Ohmiya N, et al. Efficacy of rebamipide for diclofenacinduced small-intestinal mucosal injuries in healthy subjects: a prospective, randomized, double-blinded, placebo-controlled, crossover study. J Gastroenterol. 2008;43(4):270-6. doi:10.1007/s00535-007-2155-4. Epub 2008 May 6.

Naito Y, Yoshikawa T, Iinuma S, et al. Rebamipide protects against indomethacininduced gastric mucosal injury in healthy volunteers in a double-blind, placebo-controlled study. Dig Dis Sci. 1998 Sep;43(9 Suppl): 83S-89S.

Mizukami K, Murakami K, Abe T, et al. Aspirin-induced small bowel injuries and the preventive effect of rebamipide. World J Gastroenterol. 2011 Dec 14;17(46):5117-22. doi:10.3748/wjg.v17.i46.5117.

Tozawa K, Oshima T, Okugawa T, et al. A randomized, double-blind, placebo-controlled study of rebamipide for gastric mucosal injury taking aspirin with or without clopidogrel. Dig Dis Sci. 2014 Aug;59(8):1885-90.

Kurokawa S, Katsuki S, Fujita T, et al. A randomized, double-blinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury. J Gastroenterol. 2014 Feb;49(2):239-44. doi:10.1007/s00535-013-0805-2. Epub 2013 Apr 18.

Watanabe T, Takeuchi T, Handa O, et al. A multicenter, randomized, double-blind, placebo-controlled trial of high-dose rebamipide treatment for low-dose aspirininduced moderate-to-severe small intestinal damage. PLoS One. 2015 Apr 15;10(4): e0122330. doi:10.1371/journal.pone.0122330. eCollection 2015.

Du Y, Li Z, Zhan X, et al. Anti-inflammatory effects of rebamipide according to Helicobacter pylori status in patients with chronic erosive gastritis: a randomized sucralfate-controlled multicenter trial in ChinaSTARS study. Dig Dis Sci. 2008 Nov;53(11):2886-95. doi:10.1007/s10620-007-0180-z. Epub 2008 Feb 21.

Song KH, Lee YC, Fan DM, et al. Healing effects of rebamipide and omeprazole in Helicobacter pylori-positive gastric ulcer patients after eradication therapy: a randomized double-blind, multinational, multi-institutional comparative study. Digestion. 2011;84(3):221-9. doi:10.1159/000329353. Epub 2011 Jul 8.

Terano A, Arakawa T, Sugiyama T, et al. Rebamipide, a gastro-protective and antiinflammatory 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 Aug;42(8):690-3. Epub 2007 Aug 24.

Kamada T, Sato M, Tokutomi T, et al. Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study. Biomed Res Int. 2015;2015:865146. doi:10.1155/2015/865146. Epub 2015 Apr 28.

Han X, Jiang K, Wang B, et al. Effect of rebamipide on the premalignant progression of chronic gastritis: a randomized controlled study. Clin Drug Investig. 2015 Oct;35(10):665-73. doi:10.1007/s40261-015-0329-z.

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. Dig Dis Sci. 2010 Dec;55(12):3393-8. doi:10.1007/s10620-010-1166-9. Epub 2010 Mar 3.

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 Jun 13. doi:10.5009/gnl15537. [Epub ahead of print]

Wang J, Guo X, Ye C, et al. Efficacy and safety of proton pump inhibitors (PPIs) plus rebamipide for endoscopic submucosal dissection-induced ulcers: a meta-analysis. Intern Med. 2014;53(12):1243-8. Epub 2014 Jun 15.

Nishizawa T, Suzuki H, Kanai T, Yahagi N. Proton pump inhibitor alone vs proton pump inhibitor plus mucosal protective agents for endoscopic submucosal dissection-induced ulcer: a systematic review and meta-analysis. J Clin Biochem Nutr. 2015 Mar;56(2):85-90. doi:10.3164/jcbn.14-101. Epub 2014 Dec 27.

Matsuda T, Ohno S, Hirohata S, et al. Efficacy of rebamipide as adjunctive therapy in the treatment of recurrent oral aphthous ulcers in patients with Behcet's disease: a randomised, double-blind, placebo-controlled study. Drugs R D. 2003;4(1):19-28.

Makiyama K, Takeshima F, Hamamoto T. Efficacy of rebamipide enemas in active distal ulcerative colitis and proctitis: a prospective study report. Dig Dis Sci. 2005 Dec;50(12): 2323-9.

Furuta R, Ando T, Watanabe O, et al. Rebamipide enema therapy as a treatment for patients with active distal ulcerative colitis. J Gastroenterol Hepatol. 2007 Feb;22(2):261-7.

Kashima T, Itakura H, Akiyama H, Kishi S. Rebamipide ophthalmic suspension for the treatment of dry eye syndrome: a critical appraisal. Clin Ophthalmol. 2014 May 30;8:1003-10. doi:10.2147/OPTH.S40798. eCollection 2014.

Moon SJ, Park JS, Jeong JH, et al. Augmented chondroprotective effect of coadministration of celecoxib and rebamipide in the monosodium iodoacetate rat model of osteoarthritis. Arch Pharm Res. 2013 Jan;36(1):116-24. doi:10.1007/s12272-013-0010-0.

Wood RC, Wyatt JE, Bullins KW, et al. Effects of rebamipide on nephrotoxicity associated with selected NSAIDs in rats. Eur J Pharmacol. 2013 Nov 15;720(1-3):138-46. doi:10.1016/j.ejphar.2013.10.035. Epub 2013 Oct 24.

Satoh H, Takeuchi K. Management of NSAID/aspirin-induced small intestinal damage by GI-sparing NSAIDs, anti-ulcer drugs and food constituents. Curr Med Chem. 2012;19(1):82-9.

The authors declare that there are no conflicts of interest present.