Efficacy of treatment with rebamipide for endoscopic submucosal dissection-induced ulcers

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.

Protective effect of Irsogladine on monochloramineinduced gastric mucosallesions in rats:a comparative study with rebamipide

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.

Enhanced bioavailability of rebamipide nanocrystal tablets:Formulation and in vitro/in vivo evaluation

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 of
18.2 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.

Anti free radical &anti inflammatory effect of rebamipide in chronic gastritis

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.