BACKGROUND: Gastritis is one of the most frequently diagnosed diseases requiring medical treatment in South Korea. Fexuprazan, a novel potassium-competitive acid blocker, has been approved for treating gastritis and erosive esophagitis. Meanwhile, rebamipide is the most commonly used mucoprotective agent for acute and chronic gastritis in real-world settings in South Korea. However, there have been no studies comparing the efficacy of these two drugs yet.
OBJECTIVE: To compare the efficacy of fexuprazan with that of rebamipide for acute and chronic gastritis.
METHODS: This was a matching-adjusted indirect comparison. Individual patient data from a phase III study of fexuprazan (10 mg BID) were compared with cumulative data from two matching studies of rebamipide (100 mg TID). Erosion improvement and healing rates were compared between two weeks of fexurapan, two weeks of rebamipide, and four weeks of rebamipide. The two main outcome variables were presented as percentages, and the risk differences (RD) and 95% confidence intervals (CI) were calculated for the relative treatment effects.
RESULTS: In the primary analysis, the erosion improvement and healing rates after a two-week treatment with fexuprazan were 64.5% and 53.2%, respectively, while a two-week treatment with rebamipide resulted in erosion improvement and healing rates of 43.6% (RD: 21.0%; 95%CI: 9.6-32.3; P < 0.01) and 35.6% (RD: 17.6%; 95%CI: 6.1-29.2; P = 0.003), respectively. In the additional analysis, the erosion improvement and healing rates for the two-week fexuprazan treatment (64.2% and 51.2%, respectively) were similar to those obtained during a four-week treatment with rebamipide (60.6%; RD: 3.6%; 95%CI: -9.8, 17.0; P = 0.600 and 53.5%; RD: -2.3%; 95%CI: -16.1, 11.5; P = 0.744, respectively).
CONCLUSIONS: The two-week fexuprazan treatment was superior to the two-week rebamipide treatment and similar to the four-week rebamipide treatment for patients with gastritis.

OBJECTIVE: 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.
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.
CONCLUSIONS: 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.
BACKGROUND: The trial was registered in the protocol Registration and Result system of Clinical Trials (Registration ID: NCT04685395)0.28-12-2020.

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.

Introduction The research aimed to develop a robust, high-performance liquid chromatography (HPLC) analytical method for the quantitative assessment of rebamipide encapsulated in ethosomes. Rebamipide, a quinolinone derivative, holds promise as a therapeutic agent for dry eye, but challenges such as low bioavailability and vision clouding post-installation have prompted innovative approaches. Encapsulation in ethosomes, lipid-based nanovesicles, offers a potential solution to enhance ocular bioavailability. Materials and methods The study focused on creating a specific, linear, accurate, precise, and robust HPLC method, addressing entrapment efficiency (%EE), drug content, and drug release of rebamipide in prepared ethosomes. Statistical validation followed International Conference of Harmonization (ICH) specifications. The method\'s parameters were evaluated within a concentration range of 4-24 µg/ml, with recovery rates indicating accuracy and low % relative standard deviation (RSD) values confirming precision. Limits of detection (LOD) and quantification (LOQ) for rebamipide were determined. Results After preparing the ethosome dosage form by film hydrating method for rebamipide, the rebamipide entrapment efficiency in ethosomes was established at 76% ± 7, while the drug content was found to be 93% ± 6. The drug release process demonstrated zero-order kinetics and five different models of kinetics were applied for a comprehensive analysis. The method exhibited excellent system suitability, specificity, and linearity. Recovery rates for rebamipide ranged from 90% to 100%, and repeatability was confirmed by low %RSD values. The LOD and LOQ for rebamipide were determined to be 1.04 μg/mL and 3.16 μg/mL, respectively. Conclusion The developed HPLC method proved suitable for the quantitative determination of rebamipide in ethosomes, offering rapid and accurate analysis. The results underscore the method\'s specificity, accuracy, and precision within the specified concentration range. Overall, the validated method contributes to the advancement of ocular drug delivery systems, providing a reliable analytical tool for pharmaceutical research.

UNASSIGNED: : The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage.
UNASSIGNED: : A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data.
UNASSIGNED: : The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI.
UNASSIGNED: : Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs\' potential side effects on the lower GI tract.

Recurrent aphthous stomatitis (RAS) is characterized by painful, oral mucosal ulcers with wide range of prevalence ranging from 2 to 78%. Etiology of RAS is idiopathic and multifactorial. There are numerous gaps in assessment and management of RAS and the absence of guidelines or a consensus document makes the treatment further difficult. The aim of this document is to provide an Indian expert consensus for management of RAS. Experts from different specialties such as Otorhinolaryngology, Oral Medicine/Dentistry and Internal Medicine from India were invited for face to face and online meetings. After a deliberate discussion of current literature, evidence and clinical practice during advisory meetings, experts developed a consensus for management of RAS. We identify that the prevalence of RAS may lie between 2 and 5%. In defining RAS, we advocate three or more recurrences of aphthous ulcers per year as criterion for RAS. Investigation should include basic hematological (complete blood count) and nutritional (serum vitamin B12, and iron studies) parameters. Primary aim of treatment is to reduce the pain, accelerate ulcer healing, reduce the recurrences and improve the quality of life. In treating RAS, initial choice of medications is determined by pain intensity, number and size of ulcers and previous number of recurrences. Topical and systemic agents can be used in combination for effective relief. In conclusion, this consensus will help physicians and may harmonize effective diagnosis and treatment of RAS.

Soft contact lenses are increasingly being explored as a vehicle for controlled delivery of ophthalmic drugs. However, traditional methods of drug-loading by soaking have limitations such as burst delivery and the release of drugs at the front side of the lens, leading to poor drug efficacy and systemic side effects. This study introduces a new methodology, termed asymmetric drug loading, whereby the ophthalmic drug \'Rebamipide\' is attached to and released from the post-lens (=cornea-contacting) surface exclusively. The methodology involves using polymeric microparticles that carry a lipophilic crystalline ophthalmic drug at their surface. These drug-loaded microparticles first transfer the drug to the concave surface of the contact lens, and when worn, the drug is transferred again, now from the lens to the cornea. This is achieved through the diffusion of the drug from one hydrophobic microenvironment (the silicone moieties of the contact lens polymer network) to another hydrophobic microenvironment (the corneal epithelium) over a short pathway. The second drug transfer was observed and studied in experiments using an ex vivo porcine eye model. The results show that the drug amount that was absorbed by the cornea after applying the rebamipide-loaded contact lenses is approximately 3× (10.7 ± 3.1 μg) as much as the amount of rebamipide that gets transferred after the instillation of one eye drop (1% solution (p < 0.001). The new drug-loading method offers a practical and reproducible means of delivering ophthalmic drugs to the cornea through soft contact lenses. The drug payloads achieved are comparable to dosages used during eye drop therapy.

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.
В 2022 г. в базе данных MedLine насчитывается 570 публикаций, включая 71 рандомизированное клиническое исследование и 6 метаанализов, о молекуле ребамипида. Показания к применению ребамипида – язвенная болезнь желудка, хронический гастрит с повышенной кислотообразующей функцией желудка в стадии обострения, эрозивный гастрит, профилактика повреждений слизистой оболочки желудочно-кишечного тракта на фоне приема нестероидных противовоспалительных лекарственных препаратов, эрадикация Helicobacter pylori. Изучаются эффективность и безопасность ребамипида при подагрическом и ревматоидном артритах, остеоартрите, синдроме Шегрена, бронхиальной астме, витилиго, атеросклерозе, заболеваниях почек и печени; в травматологии – для ускорения костной регенерации, в офтальмологии – для регенерации поврежденного эпителия роговицы, в онкологии – для уменьшения воспаления слизистой оболочки ротовой полости после химиолучевой терапии. В обзорной статье разбираются основные фармакокинетические и фармакодинамические характеристики ребамипида. Понимание фармакодинамики и фармакокинетики позволяет осуществлять индивидуальный подбор терапии, исходя из особенностей организма пациента (пол, возраст, сопутствующая патология); выбирать оптимальный путь введения и режим дозирования; прогнозировать нежелательные эффекты и лекарственные взаимодействия; определяться с новыми показаниями.

OBJECTIVE: 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).
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).
CONCLUSIONS: 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.
Цель. Сравнить влияние диеты с низким содержанием ферментируемых олиго-, ди-, моносахаридов и полиолов (fermentable oligosaccharides, disaccharides, monosaccharides and polyols – FODMAP) и ребамипида на переносимость углеводов и активность дисахаридаз у больных энтеропатией с нарушением мембранного пищеварения (ЭНМП). Материалы и методы. В исследование включен 61 больной ЭНМП со сниженными карбогидразами тонкой кишки. Активность глюкоамилазы по медиане у них составляла 100 нг глюкозы/мг ткани × мин (quartile 53, 72), мальтазы – 504 (quartile 258, 708), сахаразы – 43 (quartile 25, 58), лактазы – 8 (quartile 4, 20). В 1-ю группу включены 19 человек, находившихся на диете с низким содержанием FODMAP. Во 2-ю группу вошли 42 пациента, придерживавшихся обычного рациона и получавших ребамипид по 300 мг/сут. Контроль за состоянием пациентов осуществляли еженедельно на протяжении 8 нед. Результаты. У 16 лиц 1-й группы уменьшились боли в животе и нарушения стула, у 15 прекратились вздутия и урчание в животе. Активность глюкоамилазы увеличилась до 196 (quartile 133, 446, р<0,024) нг глюкозы/мг ткани × мин, мальтазы – до 889 (quartile 554, 1555, p<0,145), сахаразы – до 67 (quartile 43, 175, p<0,039), лактазы – до 13 (quartile 9, 21, p<0,02). После прекращения диеты кишечная симптоматика у пациентов 1-й группы возобновилась. У 27 участников 2-й группы через 4 нед уменьшились диспепсические проявления, у 34 улучшилась переносимость продуктов, содержащих FODMAP. Продолжение лечения до 8 нед способствовало дальнейшему улучшению самочувствия. Активность глюкоамилазы увеличилась через 4 и 8 нед до 189 (quartile 107, 357, p<0,013) и 203 (quartile 160, 536, p<0,005) соответственно; мальтазы – до 812 (quartile 487, 915, p<0,005) и 966 (quartile 621, 2195, р<0,0012); сахаразы – до 60 (quartile 34, 105, p<0013) и 75 (quartile 52, 245, р=0,003); лактазы – до 12 (quartile 8, 12, p<0,132) и 15 нг глюкозы/мг ткани × мин (quartile 10, 20, р<0,092). Заключение. При соблюдении диеты с низким содержанием FODMAP у пациентов с ЭНМП уменьшаются клинические симптомы, свойственные непереносимости ферментируемых углеводов, и повышается активность мембранных ферментов, но при переходе на обычный рацион клинические симптомы пищевой непереносимости возобновляются. При лечении ребамипидом улучшается переносимость пищевых продуктов и последовательно повышается активность ферментов СОТК через 4 и 8 нед.

Rebamipide (Reba) is a well-known gastroprotective agent. However, its potential protective efficacy against intestinal ischemia/reperfusion (I/R)-induced liver injury remains elusive. Therefore, this study aimed to assess the modulatory effect of Reba on SIRT1/β-catenin/FOXO1-NFκB signaling cascade. Thirty-two male Wistar albino rats were randomized into four groups: G1 (sham): rats were subjected to surgical stress without I/R, GII (I/R): rats were subjected to 60 min/4-h I/R, GIII (Reba + I/R): rats received Reba 100 mg/kg/day, p.o. for three weeks, then were subjected to 60 min/4-h I/R, and GIV (Reba + EX527 + I/R): rats received Reba (100 mg/kg/day p.o.) + EX527 (10 mg/kg/day, ip) for three weeks before I/R. Reba pretreatment decreased the serum levels of ALT and AST, improved I/R-induced histological alterations of both intestine and liver, increased hepatic Silent information regulator 1 (SIRT1) expression/content, β-catenin expression/immunoreactivity, and FOXO1 expression, while suppressed NF-κB p65 expression/protein content. In addition, Reba increased hepatic total antioxidant capacity (TAC), while suppressed malondialdehyde (MDA), tumor necrosis factor (TNFα), and caspase-3 activity. Furthermore, Reba inhibited BAX expression, while upregulated Bcl-2 expression. Reba exhibited a plausible protective effect against intestinal I/R-mediated liver injury by modulating SIRT1/β-catenin/FOXO1-NFκB signaling mechanisms.