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

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

doi:10.1007/s00535-007-2155-4

Cited by 123 publications

(133 citation statements)

References 27 publications

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“…In another recent clinical examination of prevention using VCE, Niwa et al [69] conducted a prospective, double-blind study using a mucosal protective agent, rebamipide, in healthy subjects. These subjects were orally administered diclofenac, omeprazole, and rebamipide for 1 week.…”

Section: Prevention and Treatment Of Small Intestinal Mucosal Injury mentioning

confidence: 99%

Present status and strategy of NSAIDs-induced small bowel injury

et al. 2009

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Non-steroidal anti-inflammatory drugs (NSAIDs) are well known to cause gastroduodenal mucosal lesions as an adverse effect. Recently, the serious problem of NSAID-induced small intestinal damage has become a topic of great interest to gastroenterologists, since capsule endoscopy and balloon enteroscopy are available for the detection of small intestinal lesions. Such lesions have been of great concern in clinical settings, and their treatment and prevention must be devised as soon as possible. The prevalence of NSAIDs-induced small intestinal injury is higher than had been expected. Recent studies show that more than 50% of patients taking NSAIDs have some mucosal damage in the small intestine. The gross appearance of NSAIDinduced enteropathy varies, appearing variously as diaphragm-like strictures, ulcers, erosions, and mucosal redness. To investigate NSAID-induced enteropathy, and to rule out other specific enteropathies, other useful methods (in addition to capsule endoscopy and balloon enteroscopy) include such modalities as radiological examination of the small intestine, the permeability test, scintigraphy or the fecal excretion test using 111 Indium-labeled white blood cells, and measurement of the fecal calprotectin concentration. Diaphragm-like strictures and bleeding from mucosal breaks may be treatable with interventional enteroscopy. Misoprostol, metronidazole, and sulfasalazine are frequently used to treat NSAID-induced enteropathy, but have undesirable effects in some cases. In the experimental model, we confirmed that several existing drugs for gastroduodenal ulcers prevented indomethacin-induced small intestinal injury. Such drugs may be useful for preventing the adverse effects of NSAIDs not only in the stomach but also in the small intestine. We hope to examine these drugs in future clinical studies.

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Section: Prevention and Treatment Of Small Intestinal Mucosal Injury mentioning

confidence: 99%

Present status and strategy of NSAIDs-induced small bowel injury

et al. 2009

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“…In a study involving healthy volunteers, rebamipide was found to be significantly more efficacious than placebo in preventing NSAID-induced injury to the mucosa of the small intestine. 6 …”

Section: Preventionmentioning

confidence: 99%

Meloxicam-induced enteropathy of the small bowel

Are

Turagam²,

Aucar³

et al. 2010

Canadian Medical Association Journal

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“…This drug has been marketed in Japan since 1990 as a therapeutic agent treating gastric ulcer and acute and/or chronic gastritis. Although the characteristics of rebamipide in preclinical and clinical area [2,3] , which is one of key factors to develop its reasonable oral dosage form at the initial stage, has been investigated fully, little was known about the permeability of this drug in different gastrointestinal tissues. On the other hand, recent studies also have shown the beneficial effect of this drug on experimental colitis.…”

Section: Introductionmentioning

confidence: 99%

Permeabilities of rebamipide via rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier

Huang¹,

Li²,

Luo³

et al. 2008

WJG

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AIM:To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol significantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10% totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng · h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng · h/mL for chitosan capsule, 1887.9 ng · h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was coadministrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rebamipide across the jejunum, ileum and the colon, and passive diffusion seems to be one of the major transport mechanisms of rebamipide. Absorption enhancers can increase the permeability of rebamipide across the colon tissue significantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifically and the coadministration of C12 with rebamipide may also be very useful in local treatment.© 2008 The WJG Press. All rights reserved.Key words: Rebamipide; Diffusion chamber; Permeability; Sodium laurate; Chitosan capsule; Colon-specific delivery Peer reviewer: Atsushi Nakajima, Professor, Yokohama City University Hospital, 3-9 Fukuura Kanazawaku, Yokohama 236, Japan Huang BB, Li GF, Luo JH, Duan L, Nobuaki K, Akira Y. Permeabilities of rebamipide via the rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier.

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

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

Cited by 123 publications

References 27 publications

Present status and strategy of NSAIDs-induced small bowel injury

Present status and strategy of NSAIDs-induced small bowel injury

Meloxicam-induced enteropathy of the small bowel

Permeabilities of rebamipide via rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier

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