Enhancing Corneal Drug Penetration Using Penetratin for Ophthalmic Suspensions.

Eye drops, including solutions and suspensions, are essential dosage forms to treat ophthalmic diseases, with poorly water-soluble drugs typically formulated as ophthalmic suspensions. In addition to low bioavailability, suspensions exhibit limited efficacy, safety, and usability due to the presence of drug particles. Improving bioavailability can reduce the drug concentrations and the risk of problems associated with suspended drug particles. However, practical penetration enhancers capable of improving bioavailability remain elusive. Herein, we focused on penetratin (PNT), a cell-penetrating peptide (CPP) that promotes active cellular transport related to macromolecule uptake, such as micropinocytosis. According to the in vitro corneal uptake study using a reconstructed human corneal epithelial tissue model, LabCyte CORNEA-MODEL24, PNT enhanced the uptake of Fluoresbrite® YG carboxylate polystyrene microspheres without covalent binding. In an ex vivo porcine eye model, the addition of 10 µM PNT to rebamipide ophthalmic suspension markedly improved the corneal uptake of rebamipide; however, the addition of 100 µM PNT was ineffective due to potentially increased particle size by aggregation. This article provides basic information on the application of PNT as a penetration enhancer in ophthalmic suspensions, including the in vitro and ex vivo studies mentioned above, as well as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay and storage stability at different pH values.

Rebamipide gargle and benzydamine gargle in prevention and management of chemo-radiotherapy and radiotherapy-induced oral mucositis in head and neck cancer patients (randomized clinical trial).

OBJECTIVES: This study aimed to evaluate the preventive and therapeutic effects of rebamipide gargle in comparison with benzydamine in head and neck cancer patients undergoing radiotherapy with or without chemotherapy. MATERIALS AND METHODS: Phase III randomized clinical trial was conducted from January 2021 till August 2022 on one hundred patients with head and neck cancer receiving high doses of radiotherapy. These patients were equally allocated into either rebamipide group or benzydamine group, The measured outcomes were the incidence of oral mucositis ≥ grade1, according to the WHO mucositis scale, in addition to the duration, and the onset of oral mucositis. RESULTS: There was no statistically significant difference between the two groups, regarding the incidence of a severe grade of oral mucositis (WHO grades 3), as well as the onset and duration of oral mucositis. Both gargles succeeded to prevent the development of WHO grade 4 oral mucositis. Side effects reported were mainly burning sensation in benzydamine group and nausea in rebamipide group. CONCLUSION: Rebamipide mouthwash was as beneficial as benzydamine mouthwash in minimizing the incidence of severe oral mucositis induced by treatment of head and neck cancer. However, rebamipide gargle proved to be superior to benzydamine in terms of reduction in the severity of the radiation-induced oral mucositis. TRIAL REGISTRATION: The trial was registered in the protocol Registration and Result system of Clinical Trials (Registration ID: NCT04685395)0.28-12-2020.

Further insights into the impact of rebamipide on gentamicin-induced nephrotoxicity in rats: modulation of SIRT1 and ß-catenin/cyclin D1 pathways.

Gentamicin (GM) is an effective antibiotic administered to treat acute Gram-negative infections. Nevertheless, its clinical application is limited due to nephrotoxicity. Therefore, our research aimed to investigate the potential renoprotective impact of rebamipide (RBM), a gastroprotective drug, on GM-induced kidney damage in rats, as well as putative nephroprotective pathways. RBM was orally administered (100 mg/kg/d for 14 d) commencing 7 d before the administration of GM (100 mg/kg/d, intraperitoneally). Nephrotoxicity was elucidated, and the silent information regulator 1 (SIRT1) and ß-catenin/cyclin D1 pathways were assessed. GM induced a significant elevation in the serum levels of creatinine, blood urea nitrogen (BUN), and kidney injury molecule-1 (KIM-1), as well as the relative kidney index. In addition, GM increased lipid peroxidation and lowered total antioxidant capacity (TAC) level and superoxide dismutase (SOD) activity. GM administration also demonstrated a significant amplification in tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), nuclear factor-κappa B p65 (NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), and caspase-3 kidney levels, as well as B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax)/Bcl-2 ratio. Notably, RBM treatment amended all these changes induced by GM. Furthermore, the potential role of SIRT1 and ß-catenin-dependent signaling pathways in GM-induced renal injury was assessed. Our findings showed that GM-treated rats demonstrated a substantial decrease in SIRT1, nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) along with an increase in ß-catenin, forkhead box O-3a (FOXO-3a), and cyclin D1 protein expressions. RMB treatment markedly attenuated the deterioration caused by GM on these pathways. Additionally, RBM alleviated the GM-induced deleterious kidney tissue histopathology. In conclusion, our findings have verified that RBM can halt GM-induced renal injury by partly modulating SIRT1 and ß-catenin pathways.

[The effect of the FODMAP and rebamipid diet on the activity of disaccharidases in patients with enteropathy with impaired membrane digestion].

AIM: To compare the effect of a diet low in fermentable oligo-, di-, monosaccharides and polyols (fermentable oligosaccharides, disaccharides, monosaccharides and polyols - FODMAP) and rebamipide on carbohydrate tolerance and disaccharidases activity in patients with maldigestive enteropathy (ENMP). MATERIALS AND METHODS: The study included 61 patients with ENMP with reduced small intestine carbohydrases. Their glucoamylase activity was 100 ng glucose/mg tissue × min (quartile 53, 72), maltase - 504 (quartile 258, 708), sucrase - 43 (quartile 25, 58), lactase - 8 (quartile 4, 20). Group 1 included 19 people on a low FODMAP diet. The 2nd group included 42 patients who were on a normal diet and received rebamipide 300 mg/day. Patients were monitored weekly for 8 weeks. RESULTS: In 16 patients of the 1st group, abdominal pain and stool disorders decreased, in 15 patients, swelling and rumbling in the abdomen stopped. Glucoamylase activity increased to 196 (quartile 133, 446, р<0.024) ng glucose/mg tissue × min, maltase activity increased to 889 (quartile 554, 1555, p<0.145), sucrase activity increased to 67 (quartile 43, 175, p<0.039), lactase activity increased to 13 (quartile 9, 21, p<0.02). After the diet was discontinued, intestinal symptoms in patients of group 1 resumed. In 27 patients of the 2nd group after 4 weeks dyspeptic manifestations decreased, in 34 patients the tolerability of products containing FODMAP improved. Continuation of treatment up to 8 weeks contributed to a further improvement in well-being. Glucoamylase activity increased after 4 and 8 weeks to 189 (quartile 107, 357, p<0.013) and 203 (quartile 160, 536, p<0.005), respectively; maltase - up to 812 (quartile 487, 915, p<0.005) and 966 (quartile 621, 2195, р<0.0012); sucrases - up to 60 (quartile 34, 105, p<0.013) and 75 (quartile 52, 245, р=0.003); lactase - up to 12 (quartile 8, 12, p<0.132) and 15 ng glucose/mg tissue × min (quartile 10, 20, р<0.092). CONCLUSION: The clinical symptoms of fermentable carbohydrate intolerance and increased membrane enzyme activity are reduced by a low FODMAP diet in patients with ENMT, but clinical symptoms of food intolerance reappear when switching to a normal diet. Treatment with rebamipide improves food tolerance and consistently increases the activity of TSOTS enzymes after 4 and 8 weeks.

[Pharmacokinetics and pharmacodynamics of rebamipide. New possibilities of therapy: A review].

The MedLine database contains 570 publications, including 71 randomized clinical trials and 6 meta-analyses on the rebamipide molecule in 2022. Indications for the use of rebamipide are gastric ulcer, chronic gastritis with hyperacidityin the acute stage, erosive gastritis, prevention of damage to the gastrointestinal mucosa while taking non-steroidal anti-inflammatory drugs, eradication of Helicobacter pylori. Currently trials are studying the efficacy and safety of the drug in gouty and rheumatoid arthritis, osteoarthritis, Sjögren's syndrome, bronchial asthma, vitiligo, atherosclerosis, diseases of the kidneys and liver; using in traumatology to accelerate bone regeneration; in ophthalmology to improve the regeneration of corneal epithelium; in oncology to reduce inflammatory changes in the oral mucosa after chemoradiotherapy. The review article is about the main pharmacokinetic and pharmacodynamic characteristics of rebamipide. A detailed understanding of pharmacodynamics and pharmacokinetics allows for individual selection of therapy based on the characteristics of the patient's body - gender, age, comorbidities; choose the optimal route of administration and dosing regimen; predict adverse effects and drug interactions; be determined with new clinical indications.

Rebamipide for the Improvement of Gastric Atrophy and Intestinal Metaplasia: A Prospective, Randomized, Pilot Study.

BACKGROUND: The presence of atrophic gastritis (AG) and intestinal metaplasia (IM) is associated with an increased risk of gastric cancer (GC). Thus, the development of new strategies to improve AG/IM is essential for reducing the incidence of GC. AIMS: We aimed to evaluate the efficacy of rebamipide for improving AG/IM. METHODS: This was a prospective, randomized, pilot study from a single tertiary referral center. Fifty-three (rebamipide, n = 34 vs. placebo, n = 19) patients, who underwent endoscopic resection for gastric dysplasia or early GC, were analyzed. We obtained tissue samples from the antrum and corpus of the stomach, at the time of screening and 1-year later. The histologic grading of inflammation was performed by histopathologists RESULTS: The AG grade in the antrum improved significantly after rebamipide treatment (pre-administration, 1.870 ± 0.932 vs. post-administration, 1.430 ± 0.986; P = 0.013). Additionally, the severity of IM in the antrum was significantly improved (pre-administration, 1.750 ± 0.963 vs. post-administration, 1.370 ± 1.032; P = 0.038). The rebamipide subgroup analysis revealed that patients with no Helicobacter pylori (HP) infection showed significant improvements in AG in the antrum (pre-administration, 1.880 ± 1.040 vs. post-administration, 1.250 ± 0.894; P = 0.028) and IM in antrum (pre-administration, 1.840 ± 1.012 vs. post-administration, 1.180 ± 0.912; P = 0.020). CONCLUSIONS: This study demonstrated that the administration of rebamipide improves AG and IM in the antrum, especially in patients with HP non-infection (KCT0001915).

[Erosive and ulcerative lesions of the digestive tract: optimization of diagnosis and management tactics].

Erosive and ulcerative lesions of the digestive tract are one of the most pressing problems in the clinic of internal diseases due to the extremely widespread prevalence, the presence of severe complications, often fatal, diagnostic difficulties due to the presence of a large number of asymptomatic pathologies and difficulties in the rational choice of therapy. Particularly noteworthy is the data that during the global pandemic of Covid-19 infection, it is capable, quite often, of causing the development of erosive and ulcerative lesions of the gastrointestinal tract. In this regard, it seems important to use drugs that can not only prevent the occurrence of erosive and ulcerative lesions and strictures throughout the gastrointestinal tract, but also effectively achieve epithelialization of injuries to the mucous membrane of the oral cavity, esophagus, stomach, small and large intestine. One of them is Rebamipid-CZ, which has a fairly high safety and efficacy profile. It seems important to consider the issues of optimizing the prevention and treatment of erosive and ulcerative lesions of various parts of the gastrointestinal tract of various etiologies, taking into account the possibility of using rebamipide both as part of complex therapy and in isolation.

[Epithelial protective therapy in comorbid diseases. Practical Guidelines for Physicians].

This document was produced with the support of the National Medical Association for the Study of Comorbidities (NASС). In 2021 the first multidisciplinary National Consensus on the pathophysiological and clinical aspects of Increased Epithelial Permeability Syndrome was published. The proposed guidelines are developed on the basis of this Consensus, by the same team of experts. Twenty-eight Practical Guidelines for Physicians statements were adopted by the Expert Council using the "delphic" method. Such main groups of epithelial protective drugs as proton pump inhibitors, bismuth drugs and probiotics are discussed in these Guidelines from the positions of evidence-based medicine. The clinical and pharmacological characteristics of such a universal epithelial protector as rebamipide, acting at the preepithelial, epithelial and subepithelial levels, throughout gastrointestinal tract, are presented in detail.

Strengthened rebamipide ocular nanoformulation to effectively treat corneal alkali burns in mice through the HMGB1 signaling pathway.

Corneal alkali burns are a major ophthalmic emergency, as current therapeutic treatments are limited. Novel treatment targets and new potential agents are required to combat this severe ocular injury. Glycyrrhizin and rebamipide (RBM) are both FDA-approved drugs with potential effects against corneal alkali burns, but RBM is limited by its low aqueous solubility and low bioavailability. This study aimed to utilize dipotassium glycyrrhizinate (DG, a dipotassium salt of glycyrrhizin) as a nanocarrier encapsulating RBM to formulate an ophthalmic solution (marked DG-RBM) with strengthened activities to treat corneal alkali burns. Results showed that an easy DG-RBM preparative process generated particles with high encapsulation efficacy and ultra-small micellar size. The solubility of RBM in DG-RBM in aqueous solution was 3.1 × 105-fold enhanced than its free solution. DG-RBM exhibited excellent storage stability. In vitro cytotoxicity, ex vivo conjunctival responses, and rabbit eye tolerance tests showed that DG-RBM possessed good ocular safety profiles. DG-RBM exhibited improved in vivo corneal permeation profiles and demonstrated a strong effect against H2O2-induced oxidative damage, with a significant effect on promoting epithelial wound healing in corneal cells in vitro. As expected, in a mouse model of corneal alkali burns, the topical administration of DG-RBM achieved a strengthened efficacy against alkali burn damages. The mechanism of this therapeutic effect involved regulating high-mobility group box 1 (HMGB1) signaling and its related angiogenic and proinflammatory cytokines. These findings demonstrate the ease of preparing DG-RBM and its great potential as a novel ocular topical formulation to treat corneal alkali burns by regulating HMGB1 signaling.

Engineering a Remedy to Modulate and Optimize Biopharmaceutical Properties of Rebamipide by Synthesizing New Cocrystal: In Silico and Experimental Studies.

PURPOSE: Rebamipide (REB) a potent anti-ulcer agent, has not been exploited to its full potential, owing to it extremely poor solubility, leading to highly diminutive bioavailability (<10%). The purpose is to carry out its solid-state modification. METHOD: Cocrystallisation was done with three GRAS coformers namely citric acid (CA), 3,4-dihydroxybenzoic acid (DHBA) and oxalic acid (OXA) employing the liquid-assisted grinding method. Cocrystal formation was based upon amide-carboxyl and amide-hydroxyl supramolecular synthons. Characterization of novel cocrystals i.e. RCA, RDHBA and ROXA was carried out by DSC, PXRD and additionally by FT-IR spectroscopy. Chemical structures have been determined utilizing the PXRD pattern by Material Studio®. Furthermore, cocrystals were subjected to solubility and intrinsic dissolution rate (IDR) evaluation. Also, pharmacodynamic and pharmacokinetic studies were performed and compared with pure rebamipide. RESULT: The appearances of a single sharp melting endotherm in DSC, along with novel characteristic peaks in PXRD infer the existence of a new crystalline form. Shifting in characteristic vibrations in FT-IR spectroscopy supports the establishment of distinct hydrogen-bonded networks. Structural determination revealed that RCA crystallizes in 'Bb2b' space groups whereas RDHBA in 'P1' and ROXA crystallize out in the 'P-1' space group. All the cocrystals exhibited superior apparent solubility and almost 7-13 folds increase in IDR. Furthermore, 1.6-2.5 folds enhancement in relative bioavailability and remarkable amplification in anti-ulcer, anti-inflammatory and the antioxidant potential of these cocrystals were observed. CONCLUSION: The study ascertains the advantages of cocrystallization, with RCA showing greatest potential and suggests a viable alternative approach for improved formulation of rebamipide.

Development of rebamipide-loaded spray-dried microsphere using distilled water and meglumine: physicochemical characterization and pharmacokinetics in rats.

In this study, a novel rebamipide-loaded spray-dried microsphere (RSM) with enhanced drug solubility and oral bioavailability has been developed utilizing meglumine, an alkalizing agent. The influence of carriers on the drug solubility alone, and the solubility and dissolution of the drug in the RSM was investigated. Among the alkalizing agents and hydrophilic polymers tested, meglumine and polyvinyl alcohol (PVA) showed the highest drug solubility and dissolution rate, respectively. Many RSMs were manufactured with various amounts of meglumine and PVA using distilled water, and their drug solubility and dissolution were determined. The physicochemical properties, dissolution and pharmacokinetics of the chosen RSM in rats were assessed compared to the rebamipide powder and commercial tablet. Among the RSMs tested, the one composed of rebamipide, meglumine and PVA at a weight ratio of 3:1.75:6 showed the highest drug solubility and dissolution. This RSM with a smooth spherical form significantly decreased the particle size and modified the amorphous rebamipide. Furthermore, the drug solubility, dissolution, plasma concentrations, AUC and Cmax values of RSM were significantly higher than those of drug powder and commercial tablet. Thus, this RSN system developed with distilled water and meglumine is recommended as an oral water-soluble rebamipide-loaded pharmaceutical product.

[Effect of rebamipide on the acute gouty arthritis in rats induced by monosodium urate crystals].

OBJECTIVE: To investigate the role of rebamipide in the treatment of acute gout arthritis rats induced by monosodium urate (MSU) crystal. METHODS: Forty-two male rats were randomly divided into three groups (n=14). Group A was treated with oral rebamipide, group B with oral colchicine, and group C with oral placebo. The rats were monitored for the induction of arthritis with clinical manifestations and pathological changes, and the levels of interleukin (IL)-1ß、IL-6、IL-10, and tumor necrosis factor (TNF)-α in serum were measured. RESULTS: In group C, the clinical score and swelling index reached the maximum in 24 h, and then gradually decreased to 72 h. After 24 h of model induced, the clinical scores in group C were significantly higher than those in group A and group B [2 (1-3) vs. 0 (0-1) vs. 1 (0-2), P < 0.01], the swelling indexes in group C were significantly higher than those in group A and group B [0.36 (0.16-0.52) vs. 0.11 (0-0.20) vs. 0.12 (0-0.16), P < 0.01]. Histologically, after 24 h of model induced, there was a large number of neutrophil infiltration in the synovium of group C [scale score: 4 (2-4)], and there was no significant inflammatory cell infiltration in group A [1 (0-2)] and group B [1 (0-2)], the difference was statistically significant (P < 0.001). After 24 h of model induced, the levels of IL-1ß, IL-6, IL-10, and TNF-α in serum of group C were significantly higher than those in group A and B [IL-1ß: (41.86±5.72) vs. (27.35±7.47) vs. (27.76±5.28) ng/L, IL-6: (1 575.55±167.11) vs. (963.53±90.22) vs. (964.08±99.31) ng/L, IL-10: (37.96±3.76) vs. (21.68±4.83) vs. (16.20±2.49) ng/L, TNF-α: (21.32±1.34) vs. (15.82±2.54) vs. (17.35±7.47) µg/L, P < 0.001]. CONCLUSION: Rebamipide has a protective effect on acute gout arthritis rats induced by MUS crystals.

Interspecies differences on pharmacokinetics of rebamipide following oral administration to rats and dogs.

Rebamipide is used widely in East Asia for the treatment of gastric ulcers, acute gastritis, and exacerbated chronic gastritis. The objective of this study was to investigate the pharmacokinetic (PK) properties of rebamipide following single oral administration in rats and dogs. Eleven rats and dogs received single oral administrations of rebamipide (35 mg/kg and 100 mg, respectively). Blood samples were collected according to the assigned schedule, and the plasma concentration of rebamipide was determined using liquid chromatography-tandem mass spectrometry. A double-peak phenomenon was observed in the PK profile of rebamipide in rats. In contrast, rebamipide showed a conventional PK profile without double peaks in dogs. The half-life of rebamipide in rats (12.85 ± 7.86 h) was longer than that in dogs (5.62 ± 2.24 h), and the apparent total clearance (Clt /F) of rebamipide in rats (3.32 ± 1.18 L/h) was lower than that in dogs (105.01 ± 42.37 L/h). Simple allometric approaches showed that the correlation between body weight and Clt /F (R2 = 0.9287) among rats, dogs, and humans appeared satisfactory. This finding will help not only in understanding the pharmacology of rebamipide but also in establishing a strategy for in vivo evaluation of novel rebamipide formulations.

Hepatoprotective effect of rebamipide against methotrexate-induced hepatic intoxication: role of Nrf2/GSK-3ß, NF-κß-p65/JAK1/STAT3, and PUMA/Bax/Bcl-2 signaling pathways.

OBJECTIVES: The fact that methotrexate (MTX) is hepatotoxic is an important reason to limit its clinical use. Rebamipide (REB) has antioxidant and anti-inflammatory properties and is useful for the treatment of gastro-duodenal ulcers. This study investigated the impact and protective mechanisms of REB against MTX-induced hepatotoxicity in rats. MATERIALS AND METHODS: Animals were divided into four groups of six rats each: a control group, REB group (REB 100 mg/kg/day, orally), MTX control group (20 mg/kg, single i.p.), and MTX + REB group. RESULTS: The administration of MTX induced marked hepatic injury in the form of hepatocyte inflammatory swelling, degeneration, apoptosis, and focal necrosis. In parallel, our biochemical investigations revealed a marked hepatic dysfunction associated with the disturbance of the oxidant/antioxidant balance in the group treated with only MTX. Moreover, MTX led to the down-regulation of the hepatic Nrf2 and Bcl-2 expressions along with a marked elevation in the hepatic NF-κß-p65, GSK-3ß, JAK1, STAT3, PUMA, and Bax expressions. On the other hand, co-treatment with REB significantly ameliorated the aforementioned histopathological, biochemical, and molecular defects caused by MTX treatment. CONCLUSION: the outcomes of the present study showed REB's ability to protect from hepatic injury induced by MTX, possibly through its antioxidant, anti-inflammatory, and anti-apoptotic properties. These effects could be attributed to REB's ability to modulate, at least in part, the Nrf2/GSK-3ß,NF-κß-p65/JAK1/STAT3, and PUMA/Bax/Bcl-2signaling pathways.

Intra-articular injection of rebamipide prevents articular cartilage degeneration in murine post-traumatic osteoarthritis models.

Objectives: Rebamipide is a protective drug used for gastric mucosal injuries, and it also exerts protective effects for a variety of other tissues. In this study, murine post-traumatic (PT) osteoarthritis (OA) models in vivo and human OA chondrocytes in vitro were used to examine the effects of rebamipide on articular cartilage degeneration.Methods: Male BALB/c mice were used. The knee ligaments were transected in both knees. Mice were injected with rebamipide into the knee joint every week. Human chondrocytes were stimulated with IL-1ß, then treated with or without rebamipide. The levels of mRNA expression of COL2A, IL-1ß, TNFα, NF-κB, MMP3, MMP13, ADAMTS5, TIMP3, FGF2, and TGFß were estimated using real-time PCR.Results: Histological scores were significantly better in the rebamipide 1 mg/mL and 10 mg/mL groups than in the control group. Rebamipide up-regulated the mRNA expressions of COL2A, TIMP3, TGFß, and FGF2 in chondrocytes and down-regulated IL-1ß, TNFα, NF-κB, MMP3, MMP13, and ADAMTS5.Conclusion: Intra-articular injection of rebamipide prevents articular cartilage degeneration for 6 weeks in murine models of OA in vivo. Rebamipide down-regulates inflammatory cytokines and catabolic factors and up-regulates anabolic factors in human chondrocytes in vitro. Rebamipide could be an important treatment for prevention of articular cartilage degeneration.

[Rebamipide using in gastroesophageal reflux disease treatment].

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.

[Pharmacological and clinical feature of rebamipide: new therapeutic targets].

Rebamipide is a cytoprotector developed in Japan where it has been successfully used for the treatment of stomach diseases for 30 years. Initially discovered effects of the drug included the induction of prostaglandins and the elimination of free oxygen radicals. Recent studies discovered new therapeutic targets of the drug, its new forms that made possible using rebamipid for the treatment of such diseases as NSAID enteropathy, ulcerative colitis, radiation colitis, pouchitis, enteropathy with impaired membrane digestion. It is used in endoscopy, ophthalmology, chemotherapy, rheumatology. The aim of this review is to present current information about the pharmacological and clinical feature of rebamipide and to study its therapeutic potential.

[Rebamipide: evidence base for use in gastroenterology].

Rebamipide is a cytoprotective drug that has been used in practical gastroenterology for 30 years. This article summarizes the main results of the most relevant clinical studies of rebamipide in diseases of various parts of the gastrointestinal tract, including the esophagus, stomach, small and large intestine.

[A new approach to understanding the pathogenesis and treatment of infectious and inflammatory diseases of the urogenital tract].

The current trends in understanding the pathogenesis of infectious and inflammatory urogenital disorders are highlighted in the review. The etiological and pathogenetic significance of increased intestinal permeability for pathogens in the development of various diseases has been convincedly proved. There is no doubt about the pathogenetic role of increased permeability of the bladder mucosa, which can result in interstitial cystitis (IC). The association of intestinal diseases with IC has been established. In rats, the induction of intestinal inflammation may cause increased permeability of the bladder mucosa. In the postoperative period, bacteria are translocated from the gastrointestinal tract to the urinary tract, which is associated with stress. Particular attention is paid to the therapy based on new knowledge about the pathogenesis of infectious and inflammatory diseases of the urogenital tract. Possibilities of decreasing intestinal and bladder permeability using rebamipide are described. Various therapeutic mechanisms of action made it possible to use this drug in endoscopy, ophthalmology, chemotherapy and rheumatology. The antioxidant and anti-inflammatory properties of rebamipide has been shown in-vitro. Intravesical instillation of rebamipide accelerates the recovery of damaged urothelium and its barrier function, and also influences on bladder hyperactivity. Thus, the first results of using rebamipide in urology are encouraging; however, further researches are required.

Chemopreventive Effect of Rebamipide against Gastric Cancer in Patients who undergo Endoscopic Resection for Early Gastric Neoplasms: A Nationwide Claims Study.

BACKGROUND/AIMS: Previous studies have shown that rebamipide is potentially protective against gastric cancer; however, no epidemiologic studies of its chemopreventive effects in patients who have a high risk of gastric cancer have been performed. The aim of this study was to investigate whether rebamipide administration reduces the risk of gastric cancer. METHODS: We conducted a population-based cohort study using data retrospectively collected from the Health Insurance Review and Assessment Service database in Korea. Patients who underwent endoscopic submucosal dissection (ESD) for early gastric neoplasms between 2011 and 2014 were included. RESULTS: During 73,416 person-years of follow-up, 711 patients were newly diagnosed with gastric cancer, including 377 low-dose (below median) and 334 high-dose (above median) rebamipide users (37,157.4 and 36,258.3 per 100,000 person-years, respectively; log-rank test, p = 0.052). There were significant differences in gastric cancer incidence rates according to age, sex, and initial diagnosis at the time of index ESD. After adjusting for these clinical factors, high-dose use was associated with a reduced risk of gastric cancer (hazard ratio 0.858; 95% CI 0.739-0.995, p = 0.043). CONCLUSION: High-dose rebamipide is associated with reduced gastric cancer risk in high-risk populations who undergo endoscopic resection for early gastric neoplasms.