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 erosi...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.AIM 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 twoweek treatment with fexuprazan were 64.5%and 53.2%,respectively,while a twoweek 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).CONCLUSION The two-week fexuprazan treatment was superior to the two-week rebamipide treatment and similar to the fourweek rebamipide treatment for patients with gastritis.展开更多
AIM:To prospectively compare the healing rates of endoscopic submucosal dissection(ESD)-induced ulcers treated with either a proton-pump inhibitor(PPI)or rebamipide.METHODS:We examined 90 patients with early gastric c...AIM:To prospectively compare the healing rates of endoscopic submucosal dissection(ESD)-induced ulcers treated with either a proton-pump inhibitor(PPI)or rebamipide.METHODS:We examined 90 patients with early gastric cancer who had undergone ESD.All patients were administered an intravenous infusion of the PPI lansoprazole(20 mg)every 12 h for 2 d,followed by oral administration of lansoprazole(30 mg/d,5 d).After7-d treatment,the patients were randomly assigned to 2 groups and received either lansoprazole(30 mg/d orally,n=45;PPI group)or rebamipide(300 mg orally,three times a day;n=45;rebamipide group).At 4and 8 wk after ESD,the ulcer outcomes in the 2 groups were compared.RESULTS:No significant differences were noted in patient age,underlying disease,tumor location,Helicobacter pylori infection rate,or ESD-induced ulcersize between the 2 groups.At both 4 and 8 wk,the healing rates of ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated patients(4 wk:PPI,27.2%;rebamipide,33.3%;P=0.5341;8 wk:PPI,90.9%;rebamipide,93.3%;P=0.6710).At 8 wk,the rates of granulation lesions following ulcer healing were significantly higher in the PPI-treated group(13.6%)than in the rebamipide-treated group(0.0%;P=0.0103).Ulcer-related symptoms were similar in the2 treatment groups at 8 wk.The medication cost of 8-wk treatment with the PPI was 10945 yen vs 4889 yen for rebamipide.No ulcer bleeding or complications due to the drugs were observed in either treatment group.CONCLUSION:The healing rate of ESD-induced ulcers was similar with rebamipide or PPI treatment;however,rebamipide treatment is more cost-effective and prevents granulation lesions following ulcer healing.展开更多
AIM:To evaluate the influence of taking low-dose aspirin for 4 wk on small intestinal complications and to examine the preventive effect of rebamipide.METHODS:This study was conducted as a single-center,randomized,dou...AIM:To evaluate the influence of taking low-dose aspirin for 4 wk on small intestinal complications and to examine the preventive effect of rebamipide.METHODS:This study was conducted as a single-center,randomized,double-blind,cross-over,placebo-controlled study.Eleven healthy male subjects were enrolled.Each subject underwent video capsule endos-copy after 1 and 4 wk of taking aspirin and omepra-zole,along with either rebamipide or placebo therapy.The primary endpoint was to evaluate small bowel damage in healthy subjects before and after taking low-dose aspirin for 4 wk.RESULTS:The number of subjects with mucosal breaks(defined as multiple erosions and/or ulcers)were 1 at 1 wk and 1 at 4 wk on the jejunum,and 6 at 1 wk(P = 0.0061)and 7 at 4 wk on the ileum(P =0.0019).Rebamipide significantly prevented mucosal breaks on the ileum compared with the placebo group(P = 0.0173 at 1 wk and P = 0.0266 at 4 wk).CONCLUSION:Longer-term,low-dose aspirin adminis-tration induced damage in the small bowel.Rebamipide prevented this damage,and may be a candidate drug for treating aspirin-induced small bowel complications.展开更多
AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A contr...AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. RESULTS: Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. CONCLUSION: Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.展开更多
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 de...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 signifi cantly 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 co-administrated, 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 Rabamipide 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 signifi cantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifi cally and the co-administration of C12 with rebamipide may also be very useful in local treatment.展开更多
Aim: To study the effect of rebamipide added to semen samples and cryoprotectant on reactive oxygen species (ROS) production. Methods: Semen samples from 30 fertile and healthy volunteers were collected by masturbatio...Aim: To study the effect of rebamipide added to semen samples and cryoprotectant on reactive oxygen species (ROS) production. Methods: Semen samples from 30 fertile and healthy volunteers were collected by masturbation after 2 days - 3 days of abstinence. After liquefaction, the specimens were diluted with sperm wash media to a uniform density of 20×106/mL. Rebamipide was added to semen samples and cryoprotectant to a final concentration of 10 μmol/L, 30 μmol/L, 100 μmol/L or 300 μmol/L. Specimens were incubated at 37 ℃ in a 0.5 % CO2 incubator for 1 h or cryopreserved at -196 ℃ LN2 for 3 days. The sperm motility and viability and the levels of ROS and lipid peroxidation of sperm membrance were assessed before and after incubation and cryopreservation by means of computer assisted semen analyzer, eosin-nigrosin stain, chemiluminescence and thiobarbituric acid assay, respectively. Results: The sperm motility was significantly increased after incubation with 100 μmol/L and 300 μmol/L rebamipide (P<0.05). After cryopreservation, the sperm motility was significantly decreased in all concentrations (P<0.05), but the decrease was less with 100 μmol/L and 300 μmol/L rebamipide than that with other concentrations. The sperm viability showed no significant difference before and after incubation (P>0.05). The levels of ROS and lipid peroxidation in semen were significantly decreased in proportion to the concentrations of rebamipide both after incubation and cryopreservation (P<0.05). Conclusion: Rebamipide is an effective free radical scavenger in semen in vitro.展开更多
The antibiotics, metronidazole and ciprofloxacin, are the first-line treatment for pouchitis. Patients who do not respond to antibiotics or conventional medications represent a major challenge to therapy. In this repo...The antibiotics, metronidazole and ciprofloxacin, are the first-line treatment for pouchitis. Patients who do not respond to antibiotics or conventional medications represent a major challenge to therapy. In this report, we have described a successful treatment of severe refractory pouchitis with a novel agent, rebamipide, known to promote epithelial cell regeneration and angiogenesis. A 27-year-old male with ileo-anal pouch surgery presented with worsening anal pain, diarrhea, and abdominal pain. The patient was diagnosed to have pouchitis and was given metronidazole together with betamethasone enema （3.95 rag/dose）. However, despite this intensive therapy, the patient did not improve. On endoscopy, ulceration and inflammation were seen in the ileal pouch together with contact bleeding and mucous discharge. The patient was treated with rebamipide enema （150 rag/close） twice a clay for 8 wk without additional drug therapy. Two weeks after the rebamipide therapy, stool frequency started to decrease and fecal hemoglobin became negative at the 4^th wk. At the end of the therapy, endoscopy revealed that ulcers in the ileal pouch had healed with no obvious inflammation. The effect of rebamipide enema was dramatic and was maintained throughout the ll-mo follow-up. The patient continued to be in remission. No adverse effects were observed during the treatment or the follow-up period. The sustained response seen in this case with severe and refractory pouchitis indicates that agents, which promote epithelial cell growth, angiogenesis and mucosal tissue regeneration, are potential therapeutic agents for the treatment of refractory colorectal lesions.展开更多
AIM To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine (NH 2Cl) in rat stomach, in comparison with rebamipide, another antiulcer drug with cytoprotectiv...AIM To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine (NH 2Cl) in rat stomach, in comparison with rebamipide, another antiulcer drug with cytoprotective activity. METHODS AND RESULTS Oral administration of NH 2Cl (120*!mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs. Both irsogladine ( 1*!mg/*!kg - 10*!mg/*!kg , po ) and rebamipide ( 30*!mg/*!kg - 100*!mg/*!kg , po ) dose dependently prevented the development of these lesions in response to NH 2Cl, the effect of irsogladine was significant at 3*!mg/*!kg or greater, and that of rebamipide only at 100*!mg/*!kg . The protective effect of irsogladine on NH 2Cl induced gastric lesions was significantly reduced by N G nitro L arginine methyl ester (L NAME) but not by indomethacin, while that of rebamipide was significantly mitigated by indomethacin but not by L NAME. Topical application of NH 2Cl (20*!mM) caused a marked reduction of potential difference (PD) in ex vivo stomachs. This PD reduction was not affected by mucosal application of irsogladine, but significantly prevented by rebamipide. The mucosal exposure to NH 4OH (120*!mM) also caused a marked PD reduction in the ischemic stomach (bleeding from the carotid artery), resulting in gastric lesions. These ulcerogenic and PD responses caused by NH 4OH plus ischemia were also significantly mitigated by rebamipide, in an indomethacin sensitive manner, while irsogladine potently prevented such lesions without affecting the PD response, in a L NAME sensitive manner. CONCLUSION These results suggest that ① NH 2Cl generated either exogenously or endogenously damages the gastric mucosa, ② both irsogladine and rebamipide protect the stomach against injury caused by NH 2Cl, and ③ the mechanism underlying the protective action of irsogladine is partly mediated by endogenous nitric oxide, while that of rebamipide is in part mediated by endogenous prostaglandins.展开更多
The purpose of this study was to formulate rebamipide nanocrystal tablets(REB-NTs)by wet-milling technique to enhance its dissolution rate and oral bioavailability.The formulation and preparation technology were scree...The purpose of this study was to formulate rebamipide nanocrystal tablets(REB-NTs)by wet-milling technique to enhance its dissolution rate and oral bioavailability.The formulation and preparation technology were screened by single factor tests with particle size and distribution as indicators.Rebamipide nanocrystals(REB-NSs)was then achieved by freeze-dry from the prepared nanosuspensions which were characterized by differential scanning calorimetry(DSC)and x-ray powder diffraction(XRD),while the vitro dissolution and the plasma drug concentration of the nanocrystal tablets were investigated.The results indicated that the prepared nanosuspensions got an average particle size of 286 nm,PI of 0.173 and the average Zeta potential of18.2 mv.The average particle size of obtained REB-NSs’redispersibility was 278 nm,and the crystalline of REB-NSs was the same as the rebamipide bulk drug as shown by DSC and XRD.The drug dissolution rate of self-made nanocrystal tablets in different dissolutions was slightly faster than that from the reference tablets,REB-MTs(Mucosta®),while the Cmax and AUC0e24 of REB-NTs were 1 and 1.57 times higher than that of REB-MTs,which means the nanotechnology could significantly improve the oral bioavailability of rebamipide.展开更多
AIM:To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro.METHODS:Acute colitis was induced with trinitrobenzene sulfonic acid(TNBS)in male Wistar ...AIM:To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro.METHODS:Acute colitis was induced with trinitrobenzene sulfonic acid(TNBS)in male Wistar rats.Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration.The distal colon was removed to evaluate the various parameters of inflammation.Moreover,wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial(RIE)cells treated with rebamipide.RESULTS:Intracolonic administration of rebamipide accelerated TNBSinduced ulcer healing.Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide.The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signalregulated kinase(ERK)and activation of Rho kinase.CONCLUSION:Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells,via ERK activation.Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.展开更多
Background/Aim: Free radicals have a role in the development of chronic gastritis. The aim of this study to know the effect and efficacy of rebamipide on free radicals in chronic gastritis. Method: Forty five patients...Background/Aim: Free radicals have a role in the development of chronic gastritis. The aim of this study to know the effect and efficacy of rebamipide on free radicals in chronic gastritis. Method: Forty five patients in the division gastroenterology Cipto Mangunkusumo Hospital Jakarta 2009-2010 with moderate and severe gastritis endoscopically were included in this study. Before and after rebamipide treatment the patient were performed endoscopical examination and were taken 5 biopsies for histopathological examination and free radicals (MDA & Carbonyl Compound) examination. All patients were given rebamipide 100 mg three times a day for 28 days. Data were analyzed with t test or wilcoxon signed rank test. Exclusion: GERD, Peptic ulcer, PPI treatment, NSAID consumption etc. The symptoms were recorded on day-0 and day-28. The severity symptoms were measured by VAS. Result: The mucosal damage on day-0 was 2.268 ± 0.45 vs day-28 was 1.707 ± 0.78 (P < 0.001). The antrum neutrophil: day-0: 0.12 ± 0.46 vs day-28: 0.10 ± 0.37 (P = 0.710) and corpus neutrophil: day-0: 0.12 ± 0.40 vs day-28: 0.07 ± 0.26 (P = 0.421). The mean endoscopical mucosal severity score was decreased significantly on day- 28 compared to day-0 (1.707 ± 0.78 vs 2.268 ± 0.45;P < 0.05). The other histopathological appearances between day-0 and day-28 were not different. Rebamipide can reduce the mean of MDA from 5.28 ± 3.54 on day-0 to 4.15 ± 2.71 on day-28 (P = 0.047). The mean of carbonyl compound on day-0 was 4.14 ± 3.01 and on day-28 was 5.12 ± 2.71 (P = 0.642). Conclusion: Rebamipide significantly reduced the extend of symptoms associated with chronic gastritis. The improvement in symptoms was associated with the decreased of endoscopic severity score and the mean gastric mucosal malondialdehyde (MDA) significantly but not the histopathologic appearance and carbonyl compound.展开更多
The objective of this study was to investigate the pantoprazole and rebamipide efficiency on NSAIDs （nonsteroidal anti-inflammatory drugs）-gastropathy restoring and healing in patients with coronary heart disease, s...The objective of this study was to investigate the pantoprazole and rebamipide efficiency on NSAIDs （nonsteroidal anti-inflammatory drugs）-gastropathy restoring and healing in patients with coronary heart disease, stable angina, who have been taking aspirin for a long time period. The study included three groups of patients according to the treatment they have got： ASA （acetylsalicylic acid） in the first group; ASA and pantoprazole in the second; ASA, pantoprazole and rebamipide in the third one. To obtain the results, endoscopic method and proinflammatory cytokines LTB4 and protective prostaglandin E2 determination in the blood were used. The research demonstrated no ulcer effects in the group of patients who were treated by rebamipide, and significantly fewer gastroduodenal erosions, in comparison to the group, where treatment contained ASA and pantoprazole. The LTB4 （leukotriene B4） level decreased in pantoprazole and rebamipide treatment groups, but the PGE2 （prostaglandin E2） level increased only after rebamipide therapy. Therefore, rebamipide should be included to the therapy for the better NSAIDs-gastropathy treatment, in reason of its good reparative and gastroprotective properties.展开更多
AIM:To investigate the relationship between low-dose aspirin-induced small bowel mucosal damage and blood flow,and the effect of rebamipide. METHODS:Ten healthy volunteers were enrolled in this study.The subjects were...AIM:To investigate the relationship between low-dose aspirin-induced small bowel mucosal damage and blood flow,and the effect of rebamipide. METHODS:Ten healthy volunteers were enrolled in this study.The subjects were divided into two groups:a placebo group given low-dose aspirin plus placebo and a rebamipide group given low-dose aspirin plus rebamipide for a period of 14 d.Capsule endoscopy and contrast-enhanced ultrasonography were performed before and after administration of drugs.Areas under the curves and peak value of time-intensity curve were calculated. RESULTS:Absolute differences in areas under the curves were-1102.5(95%CI:-1980.3 to-224.7,P=0.0194) in the placebo group and-152.7(95%CI:-1604.2 to 641.6,P=0.8172) in the rebamipide group. Peak values of time intensity curves were-148.0(95% CI:-269.4 to-26.2,P=0.0225) in the placebo group and 28.3(95%CI:-269.0 to 325.6,P=0.8343) in the rebamipide group.Capsule endoscopy showed mucosal breaks only in the placebo group. CONCLUSION:Short-term administration of low-dose aspirin is associated with small bowel injuries and blood flow.展开更多
文摘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.AIM 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 twoweek treatment with fexuprazan were 64.5%and 53.2%,respectively,while a twoweek 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).CONCLUSION The two-week fexuprazan treatment was superior to the two-week rebamipide treatment and similar to the fourweek rebamipide treatment for patients with gastritis.
文摘AIM:To prospectively compare the healing rates of endoscopic submucosal dissection(ESD)-induced ulcers treated with either a proton-pump inhibitor(PPI)or rebamipide.METHODS:We examined 90 patients with early gastric cancer who had undergone ESD.All patients were administered an intravenous infusion of the PPI lansoprazole(20 mg)every 12 h for 2 d,followed by oral administration of lansoprazole(30 mg/d,5 d).After7-d treatment,the patients were randomly assigned to 2 groups and received either lansoprazole(30 mg/d orally,n=45;PPI group)or rebamipide(300 mg orally,three times a day;n=45;rebamipide group).At 4and 8 wk after ESD,the ulcer outcomes in the 2 groups were compared.RESULTS:No significant differences were noted in patient age,underlying disease,tumor location,Helicobacter pylori infection rate,or ESD-induced ulcersize between the 2 groups.At both 4 and 8 wk,the healing rates of ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated patients(4 wk:PPI,27.2%;rebamipide,33.3%;P=0.5341;8 wk:PPI,90.9%;rebamipide,93.3%;P=0.6710).At 8 wk,the rates of granulation lesions following ulcer healing were significantly higher in the PPI-treated group(13.6%)than in the rebamipide-treated group(0.0%;P=0.0103).Ulcer-related symptoms were similar in the2 treatment groups at 8 wk.The medication cost of 8-wk treatment with the PPI was 10945 yen vs 4889 yen for rebamipide.No ulcer bleeding or complications due to the drugs were observed in either treatment group.CONCLUSION:The healing rate of ESD-induced ulcers was similar with rebamipide or PPI treatment;however,rebamipide treatment is more cost-effective and prevents granulation lesions following ulcer healing.
基金Supported by The Department of General Medicine and Gastroenterology,Oita University
文摘AIM:To evaluate the influence of taking low-dose aspirin for 4 wk on small intestinal complications and to examine the preventive effect of rebamipide.METHODS:This study was conducted as a single-center,randomized,double-blind,cross-over,placebo-controlled study.Eleven healthy male subjects were enrolled.Each subject underwent video capsule endos-copy after 1 and 4 wk of taking aspirin and omepra-zole,along with either rebamipide or placebo therapy.The primary endpoint was to evaluate small bowel damage in healthy subjects before and after taking low-dose aspirin for 4 wk.RESULTS:The number of subjects with mucosal breaks(defined as multiple erosions and/or ulcers)were 1 at 1 wk and 1 at 4 wk on the jejunum,and 6 at 1 wk(P = 0.0061)and 7 at 4 wk on the ileum(P =0.0019).Rebamipide significantly prevented mucosal breaks on the ileum compared with the placebo group(P = 0.0173 at 1 wk and P = 0.0266 at 4 wk).CONCLUSION:Longer-term,low-dose aspirin adminis-tration induced damage in the small bowel.Rebamipide prevented this damage,and may be a candidate drug for treating aspirin-induced small bowel complications.
文摘AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. RESULTS: Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. CONCLUSION: Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.
基金Research Funding of Medical Association of Japanese-Chinese, Japan
文摘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 signifi cantly 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 co-administrated, 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 Rabamipide 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 signifi cantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifi cally and the co-administration of C12 with rebamipide may also be very useful in local treatment.
文摘Aim: To study the effect of rebamipide added to semen samples and cryoprotectant on reactive oxygen species (ROS) production. Methods: Semen samples from 30 fertile and healthy volunteers were collected by masturbation after 2 days - 3 days of abstinence. After liquefaction, the specimens were diluted with sperm wash media to a uniform density of 20×106/mL. Rebamipide was added to semen samples and cryoprotectant to a final concentration of 10 μmol/L, 30 μmol/L, 100 μmol/L or 300 μmol/L. Specimens were incubated at 37 ℃ in a 0.5 % CO2 incubator for 1 h or cryopreserved at -196 ℃ LN2 for 3 days. The sperm motility and viability and the levels of ROS and lipid peroxidation of sperm membrance were assessed before and after incubation and cryopreservation by means of computer assisted semen analyzer, eosin-nigrosin stain, chemiluminescence and thiobarbituric acid assay, respectively. Results: The sperm motility was significantly increased after incubation with 100 μmol/L and 300 μmol/L rebamipide (P<0.05). After cryopreservation, the sperm motility was significantly decreased in all concentrations (P<0.05), but the decrease was less with 100 μmol/L and 300 μmol/L rebamipide than that with other concentrations. The sperm viability showed no significant difference before and after incubation (P>0.05). The levels of ROS and lipid peroxidation in semen were significantly decreased in proportion to the concentrations of rebamipide both after incubation and cryopreservation (P<0.05). Conclusion: Rebamipide is an effective free radical scavenger in semen in vitro.
文摘The antibiotics, metronidazole and ciprofloxacin, are the first-line treatment for pouchitis. Patients who do not respond to antibiotics or conventional medications represent a major challenge to therapy. In this report, we have described a successful treatment of severe refractory pouchitis with a novel agent, rebamipide, known to promote epithelial cell regeneration and angiogenesis. A 27-year-old male with ileo-anal pouch surgery presented with worsening anal pain, diarrhea, and abdominal pain. The patient was diagnosed to have pouchitis and was given metronidazole together with betamethasone enema （3.95 rag/dose）. However, despite this intensive therapy, the patient did not improve. On endoscopy, ulceration and inflammation were seen in the ileal pouch together with contact bleeding and mucous discharge. The patient was treated with rebamipide enema （150 rag/close） twice a clay for 8 wk without additional drug therapy. Two weeks after the rebamipide therapy, stool frequency started to decrease and fecal hemoglobin became negative at the 4^th wk. At the end of the therapy, endoscopy revealed that ulcers in the ileal pouch had healed with no obvious inflammation. The effect of rebamipide enema was dramatic and was maintained throughout the ll-mo follow-up. The patient continued to be in remission. No adverse effects were observed during the treatment or the follow-up period. The sustained response seen in this case with severe and refractory pouchitis indicates that agents, which promote epithelial cell growth, angiogenesis and mucosal tissue regeneration, are potential therapeutic agents for the treatment of refractory colorectal lesions.
文摘AIM To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine (NH 2Cl) in rat stomach, in comparison with rebamipide, another antiulcer drug with cytoprotective activity. METHODS AND RESULTS Oral administration of NH 2Cl (120*!mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs. Both irsogladine ( 1*!mg/*!kg - 10*!mg/*!kg , po ) and rebamipide ( 30*!mg/*!kg - 100*!mg/*!kg , po ) dose dependently prevented the development of these lesions in response to NH 2Cl, the effect of irsogladine was significant at 3*!mg/*!kg or greater, and that of rebamipide only at 100*!mg/*!kg . The protective effect of irsogladine on NH 2Cl induced gastric lesions was significantly reduced by N G nitro L arginine methyl ester (L NAME) but not by indomethacin, while that of rebamipide was significantly mitigated by indomethacin but not by L NAME. Topical application of NH 2Cl (20*!mM) caused a marked reduction of potential difference (PD) in ex vivo stomachs. This PD reduction was not affected by mucosal application of irsogladine, but significantly prevented by rebamipide. The mucosal exposure to NH 4OH (120*!mM) also caused a marked PD reduction in the ischemic stomach (bleeding from the carotid artery), resulting in gastric lesions. These ulcerogenic and PD responses caused by NH 4OH plus ischemia were also significantly mitigated by rebamipide, in an indomethacin sensitive manner, while irsogladine potently prevented such lesions without affecting the PD response, in a L NAME sensitive manner. CONCLUSION These results suggest that ① NH 2Cl generated either exogenously or endogenously damages the gastric mucosa, ② both irsogladine and rebamipide protect the stomach against injury caused by NH 2Cl, and ③ the mechanism underlying the protective action of irsogladine is partly mediated by endogenous nitric oxide, while that of rebamipide is in part mediated by endogenous prostaglandins.
文摘The purpose of this study was to formulate rebamipide nanocrystal tablets(REB-NTs)by wet-milling technique to enhance its dissolution rate and oral bioavailability.The formulation and preparation technology were screened by single factor tests with particle size and distribution as indicators.Rebamipide nanocrystals(REB-NSs)was then achieved by freeze-dry from the prepared nanosuspensions which were characterized by differential scanning calorimetry(DSC)and x-ray powder diffraction(XRD),while the vitro dissolution and the plasma drug concentration of the nanocrystal tablets were investigated.The results indicated that the prepared nanosuspensions got an average particle size of 286 nm,PI of 0.173 and the average Zeta potential of18.2 mv.The average particle size of obtained REB-NSs’redispersibility was 278 nm,and the crystalline of REB-NSs was the same as the rebamipide bulk drug as shown by DSC and XRD.The drug dissolution rate of self-made nanocrystal tablets in different dissolutions was slightly faster than that from the reference tablets,REB-MTs(Mucosta®),while the Cmax and AUC0e24 of REB-NTs were 1 and 1.57 times higher than that of REB-MTs,which means the nanotechnology could significantly improve the oral bioavailability of rebamipide.
基金Supported by A GrantinAid for Scientific Research(B)to Toshikazu Yoshikawa(Grant No.21390184)Challenging Exploratory Research to Yuji Naito(No.08101559)from the Japan Society for the Promotion of Science+1 种基金A City Area Program to Toshikazu Yoshikawa and Yuji Naito from Ministry of Education,Culture,Sports,Science and Technology,JapanAn Adaptable and Seamless Technology Transfer Program through targetdriven R&D to Yuji Naito from Japan Science and Technology Agency
文摘AIM:To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro.METHODS:Acute colitis was induced with trinitrobenzene sulfonic acid(TNBS)in male Wistar rats.Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration.The distal colon was removed to evaluate the various parameters of inflammation.Moreover,wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial(RIE)cells treated with rebamipide.RESULTS:Intracolonic administration of rebamipide accelerated TNBSinduced ulcer healing.Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide.The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signalregulated kinase(ERK)and activation of Rho kinase.CONCLUSION:Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells,via ERK activation.Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.
文摘Background/Aim: Free radicals have a role in the development of chronic gastritis. The aim of this study to know the effect and efficacy of rebamipide on free radicals in chronic gastritis. Method: Forty five patients in the division gastroenterology Cipto Mangunkusumo Hospital Jakarta 2009-2010 with moderate and severe gastritis endoscopically were included in this study. Before and after rebamipide treatment the patient were performed endoscopical examination and were taken 5 biopsies for histopathological examination and free radicals (MDA & Carbonyl Compound) examination. All patients were given rebamipide 100 mg three times a day for 28 days. Data were analyzed with t test or wilcoxon signed rank test. Exclusion: GERD, Peptic ulcer, PPI treatment, NSAID consumption etc. The symptoms were recorded on day-0 and day-28. The severity symptoms were measured by VAS. Result: The mucosal damage on day-0 was 2.268 ± 0.45 vs day-28 was 1.707 ± 0.78 (P < 0.001). The antrum neutrophil: day-0: 0.12 ± 0.46 vs day-28: 0.10 ± 0.37 (P = 0.710) and corpus neutrophil: day-0: 0.12 ± 0.40 vs day-28: 0.07 ± 0.26 (P = 0.421). The mean endoscopical mucosal severity score was decreased significantly on day- 28 compared to day-0 (1.707 ± 0.78 vs 2.268 ± 0.45;P < 0.05). The other histopathological appearances between day-0 and day-28 were not different. Rebamipide can reduce the mean of MDA from 5.28 ± 3.54 on day-0 to 4.15 ± 2.71 on day-28 (P = 0.047). The mean of carbonyl compound on day-0 was 4.14 ± 3.01 and on day-28 was 5.12 ± 2.71 (P = 0.642). Conclusion: Rebamipide significantly reduced the extend of symptoms associated with chronic gastritis. The improvement in symptoms was associated with the decreased of endoscopic severity score and the mean gastric mucosal malondialdehyde (MDA) significantly but not the histopathologic appearance and carbonyl compound.
文摘The objective of this study was to investigate the pantoprazole and rebamipide efficiency on NSAIDs （nonsteroidal anti-inflammatory drugs）-gastropathy restoring and healing in patients with coronary heart disease, stable angina, who have been taking aspirin for a long time period. The study included three groups of patients according to the treatment they have got： ASA （acetylsalicylic acid） in the first group; ASA and pantoprazole in the second; ASA, pantoprazole and rebamipide in the third one. To obtain the results, endoscopic method and proinflammatory cytokines LTB4 and protective prostaglandin E2 determination in the blood were used. The research demonstrated no ulcer effects in the group of patients who were treated by rebamipide, and significantly fewer gastroduodenal erosions, in comparison to the group, where treatment contained ASA and pantoprazole. The LTB4 （leukotriene B4） level decreased in pantoprazole and rebamipide treatment groups, but the PGE2 （prostaglandin E2） level increased only after rebamipide therapy. Therefore, rebamipide should be included to the therapy for the better NSAIDs-gastropathy treatment, in reason of its good reparative and gastroprotective properties.
基金Supported by Grant support from Daiichi Sankyo Co.,Ltd.,Astra Zeneca Co.,Ltd.,and Otsuka Pharmaceutical Co.,Ltd(To Yokosuka O)the lecture fees from Daiichi Sankyo,AstraZeneca(To Arai M)
文摘AIM: To investigate the optimum period of treatment for post endoscopic submucosal dissection (ESD) ulcers.
文摘AIM:To investigate the relationship between low-dose aspirin-induced small bowel mucosal damage and blood flow,and the effect of rebamipide. METHODS:Ten healthy volunteers were enrolled in this study.The subjects were divided into two groups:a placebo group given low-dose aspirin plus placebo and a rebamipide group given low-dose aspirin plus rebamipide for a period of 14 d.Capsule endoscopy and contrast-enhanced ultrasonography were performed before and after administration of drugs.Areas under the curves and peak value of time-intensity curve were calculated. RESULTS:Absolute differences in areas under the curves were-1102.5(95%CI:-1980.3 to-224.7,P=0.0194) in the placebo group and-152.7(95%CI:-1604.2 to 641.6,P=0.8172) in the rebamipide group. Peak values of time intensity curves were-148.0(95% CI:-269.4 to-26.2,P=0.0225) in the placebo group and 28.3(95%CI:-269.0 to 325.6,P=0.8343) in the rebamipide group.Capsule endoscopy showed mucosal breaks only in the placebo group. CONCLUSION:Short-term administration of low-dose aspirin is associated with small bowel injuries and blood flow.
