Efficacy of Ecabet Sodium for Helicobacter pylori Eradication with Sequential Therapy

BACKGROUND/AIMS: We aimed to compare the outcomes of Helicobacter pylori eradication in patients receiving sequential therapy (ST) depending on the use of ecabet sodium (ES). MATERIALS AND METHODS: Between January to December 2015, 176 patients randomly received either ST alone (n=72) or 10-day ES therapy combined with ST (n=104). After applying the exclusion criteria, 56 patients were finally assigned to the ST-only group and 84 to the ST with ES group. We retrospectively reviewed and analyzed the H. pylori eradication rate and adverse events between the two groups. RESULTS: Among the 140 patients, 121 (86.4%) achieved successful H. pylori eradication and 24 (17.1%) had adverse events. Eradication was achieved in 50 patients (89.3%) in the ST-only group and in 71 patients (84.5%) in the ST with ES group (P=0.420). No significant difference in the incidence of adverse events was found between the ST-only and ST with ES groups (12.5% vs. 20.2%, respectively; P=0.234). However, the ST with ES group tended to have a higher prevalence of nausea or vomiting than the ST-only group (11.9% vs. 1.8%; P=0.050). CONCLUSIONS: ST showed a good H. pylori eradication rate without deteriorating the adverse events regardless of adding ES.

Determination of potential genotoxic impurity in ecabet sodium active pharma-ceutical ingredient by HPLC-MS/MS / 中国药科大学学报

To develop a sensitive analytical method for the determination of the genotoxic impurity mono ethyl ester of ecabet (Imp-I),an HPLC-MS/MS technique was employed. Imp-I was synthesized according to the previ-ous literatures. MS/MS and NMR were used to confirm the structure of Imp-I. A Thermo C18column was used for chromatographic separations. The mobile phase consisting of A:5 mmol/L ammonium acetate (pH adjusted to 3. 0 with formic acid)and B:acetonitrile,with a gradient program:0 min 50%B,4 min 50%B,12 min 80%B,16 min 80%B,16. 1 min 50%B and 20 min 50%B. The column was maintained at 40 °C throughout the analysis.All measurements were carried out with the mass spectrometer operated under the negative ESI mode. The selective reaction monitor (SRM)transition was used. Good linearity was obtained for Imp-I over the concentration range of 4 150 ng/mL with the coefficient of determination (r)of 0. 999. And the LOQ was 4 ng/mL. A rapid and sensi-tive HPLC-ESI-MS/MS method was developed for quantitative analysis of Imp-I in ecabet sodium APIs. This method can be of used for quality assurance of ecabet sodium in bulk commercial drugs.

The Efficacy of Rebamipide or Ecabet Sodium Supplementation for Helicobacter pylori Eradication Therapy Compared with Quadruple (Concomitant) Regimen / 대한소화기학회지

BACKGROUND/AIMS: Although some previous studies reported that a treatment combined with mucoprotective agent could improve the eradication rate in dual or triple therapy, there are other reports that question the efficacy of combining these drugs in concomitant therapy (CoCTx). The aim of this study was to investigate the effects of rebamipide or ecabet on the Helicobacter pylori (H. pylori) eradication combined with CoCTx. METHODS: We retrospectively reviewed the medical records of 277 patients with proven H. pylori infection. They were assigned to one of 3 regimens for 10 days, twice daily: (a) CoCTx (n=118): lansoprazole 30 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg; (b) CoCTx+rebamipide (100 mg) (n=85); (c) CoCTx+ecabet (1 g) (n=74). RESULTS: The baseline characteristics were not significantly different. H. pylori eradication rates were 82.2% (97/118) in CoCTx, 90.6% (77/85) in CoCTx+rebamipide, and 89.2% (66/74) in CoCTx+ecabet (p=0.17), which were statistically insignificant. Overall adverse events were more frequently reported in the CoCTx+rebamipide (50.6%. 43/85) and CoCTx+ecabet (44.6%, 33/74) groups than in the CoCTx (32.2%, 38/118) (p = 0.03) group. Drug compliances were not different between three groups (CoCTx: 95.8%, 113/118; CoCT+rebamipide: 92.9%, 79/85; CoCTx+ecabet 98.6%,73/74) (p=0.209). Multivariate analysis showed that the risk of eradication failure was significantly increased with decreased drug compliance (odds ratio 3.52, 95% confidence interval 1.00–12.32; p=0.05). CONCLUSIONS: Addition of these mucoprotective agent was not superior to CoCTx alone for eradicating H. pylori infection with frequent adverse events. Rather, drug compliance is the most related factor affecting the eradication rate. Our data suggest the importance of drug compliance over the drugs used.

The impact of inflammatory cytokines and therapy effect of ecabet sodium quadruple therapy for patients with duodenal ulcer / 中国生化药物杂志

Objective To study the effect of inflammatory cytokines and therapy effect of ecabet sodium quadruple therapy for patients with duodenal ulcer.Methods80 cases patients with H.pylori-positive ulcer duodenal in In our hospital In our hospital April 2015 to December 2016 were randomLy divided into observation group 42 cases and control group 38 cases, the observation group were treated with ecabet sodium quadruple therapy, the control group were treated with colloidal bismuth pectin quadruple therapy.Then therapy effect, H.pylori eradication rate, inflammatory cytokines, adverse reactions were compared between two groups.ResultsUlcer healing: the observation group total effective rate 97.62% was significantly higher than the control group 78.95% (χ2=6.966, P<0.05);Hp eradicate rate: the observation group Hp eradicate rate 95.24% was significantly higher than that of control group 76.32%(χ2=6.023, P<0.05);Serum inflammatory factors: observation group serum TNF-α, IL-6, IL-8 levels were significantly lower than the control group(t =4.272, 7.584, 3.095, P<0.05);Adverse reaction: observation group adverse reactions 7.14% was significantly lower than the control group 23.68%(χ2=4.281, P<0.05).ConclusionEcabet sodium quadruple therapy helps to reduce serum inflammatory factor expression level, then improve therapy effect and reduce adverse reactions.

Determination of Residual of 4 Kinds Organic Solvents in Ecabet Sodium Crude Drug by Capillary GC / 中国药房

OBJECTIVE:To establish a method for the determination of residuals of petroleum ether,ethanol,xylene and ace-tic acid in ecabet sodium crude drug. METHODS:Capillary GC was performed on the column of PGE-20M capillary column at the flow rate of 1.7 ml/min,detector was hydrogen flame ionization detector,carrier gas was nitrogen with high purity,column temper-ature was 45 ℃,maintaining 4 min,it increased to 80 ℃ with rate of 10 ℃/min,then increased to 135 ℃ with rate of 30 ℃/min,maintaining 3 min,the injection mode was direct injection,inlet temperature was 250 ℃,and the volume injection was 1.0 μl. RESULTS:The mass concentration was 0.050-1.952 g/L for petroleum ether,0.050-1.941 g/L for ethanol,0.024-0.948 g/L for xy-lene and 0.050-1.947g/L for acetic acid(r=0.999 1-0.999 7);RSDs of precision,stability and reproducibility tests were no more than 1.7%;recoveries were 99.3%-101.0%(RSD=0.7%,n=9),102.3%-103.7%(RSD=0.4%,n=9),101.2%-102.1%(RSD=0.3%,n=9) and 100.3%-102.2%(RSD=0.6%,n=9),respectively. CONCLUSIONS:The method is simple and accurate,and can be used for the control of residual of organic solvents in ecabet sodium crude drug.

Clinical trial on ecabet sodium-based quadruple therapy for Helicobacter pylori eradication: a multicenter clinical study / 中华消化杂志

Objective To assess and compare the efficacy and safety of ecabet sodium-based quadruple therapy versus bismuth-based quadruple therapy for Helicobacter pylori (Hp) eradication.Methods A multicenter,randomized,positive controlled clinical trial was carried out.The object of the study were chronic gastritis patients at 8 hospitals in Xi'an,Beijing,Shanghai and Guangzhou from June 2009 to June 2011.All patients were divided into treatment group and control group.In treatment group,patients received ecabet sodium-based quadruple therapy (two times per day,omeprazole magnesium 20 mg,amoxicillin 1000 mg,clarithromycin 500 mg and ecabet sodium 1.0 g each time for 10 days.In control group,patients were assigned to receive bismuth-based quadruple therapy (two times per day; omeprazole magnesium 20 mg,amoxicillin 1000 mg,clarithromycin 500 mg and bismuth potassium citrate 220 mg each time) for 10 days.The Hp eradication was determined by 13C or 14C urea breath test at the 38th day after the treatment and the eradication rate was calculated.Side effects were recorded and analyzed.The data were analyzed by chi square test and Fisher's exact test.Results A total of 311 patients were recruited,and 155 patients were allatted in treatment group and 156 in control group.The per-protocol (PP) analysis indicated that the eradication rates of treatment group arid control group were 75.71％(106/140) and 77.37％(106/137) respectively,and there was no significant difference x2 =0.106,P=0.745).The intention-to-treat (ITT) analysis indicated that the eradication rates of treatment group and control group were 68.39％ (106/155) and 67.95％ (106/156) respectively,and there was no significant difference x2 =0.007,P=0.934).The side effects rates of treatment group and control group were 20.00％ (31/155) and 25.64％(40/156) respectively,and the difference was not statistically significant (Fisher's exact test,P=0.280).No serious side effect was observed in two groups.Conclusion The efficacy and safety of ecabet sodium-based quadruple therapy for Hp eradication in chronic gastritis patients may be the same as bismuth-based quadruple therapy.

Determination of ecabet and bismuth in human urine and study on their urinary excretion profiles / 中国药学杂志

OBJECTIVE: To establish an HPLC-MS method for the determination of ecabet and a HG-AFS method for the determination of bismuth, and to investigate their urinary excretion profiles after oral administration of ecabet bismuth suspension in healthy volunteers. METHODS: Urine samples were precipitated, acidized, and separated on an Hanbon ODS-2 column with methanol-20 mmol·L-1 ammonium (55:45) as a mobile phase. Electrospray ionization source and negative ion mode for MS were used. A sensitive hydride generation atomic fluorescence spectrophotometry (HG-AFS) method for the determination of bismuth was also developed and validated. Urine samples were digested using wet digestion method. Ten healthy volunteers were given single oral dose of 800 mg ecabet bismuth suspension. RESULTS: The calibration curve in urine was linear in the range of 20.44-30660 ng·mL-1 for ecabet and 0.3-40 ng·mL-1 for bismuth, respectively. The average recoveries were more than 92.8% and 92.0%, respectively. After the volunteers took the suspensions, the average urinary excretion rates of ecabet and bismuth were highest at 0-2 h and the average cumulative excretion percentages of ecabet and bismuth in urine within 72 h were (0.9±0.6)% and (0.02±0.01)%, respectively. CONCLUSION: The methods are suitable for the determination of ecabet and bismuth in human urine and for the investigation on their urinary excretion profiles. Copyright 2012 by the Chinese Pharmaceutical Association.

Efficacy of Ecabet Sodium for Helicobacter pylori Eradication, Combined with Lansoprazole-Based Triple Regimen: A Prospective Study / 대한내과학회지

BACKGROUND/AIMS: Ecabet sodium is used for treating gastric ulcers and gastritis. It exhibits a bactericidal effect against Helicobacter pylori by inhibiting bacterial urease activity. Thus, ecabet sodium has been suggested to improve the efficacy of the H. pylori eradication in patients with peptic ulcers. The aim of this study was to compare the H. pylori eradication rate of lansoprazole-based triple therapy versus lansoprazole-based triple therapy plus ecabet sodium. METHODS: The subjects consisted of 363 H. pylori-positive patients who had undergone eradication therapy from February 2007 to February 2010. In total, 363 patients with H. pylori-positive peptic ulcer disease or symptomatic erosive gastritis received LAC (lansprazole 30 mg b.i.d., amoxicillin 1.0 g b.i.d., clarithromycin 500 mg b.i.d.) or LACE (lansoprazole 30 mg b.i.d., amoxicillin 1.0 g b.i.d., clarithromycin 500 mg b.i.d., ecabet sodium 1 g b.i.d.) for 1 week. Successful eradication was defined as a negative 13Curea breath test 4-5 weeks after treatment completion. RESULTS: H. pylori eradication rates were 81.4% (166/204) in the LAC group and 86.2% (137/159) in the LACE group (p = 0.159). No significant difference in eradication was observed. No significant difference was observed in the side effects experienced by the patients in the two treatment groups. CONCLUSIONS: Our results suggest that adding ecabet sodium did not improve the H. pylori eradication rate significantly in standard lansoprazole-based triple therapy for H. pylori.

Effect of Additional Ecabet Sodium on Conventional Triple Therapy for Helicobacter pylori Eradication in Korea / 대한소화기내시경학회지

BACKGROUND/AIMS: Ecabet sodium is known for its bactericidal effect against H. pylori. It was reported that a supplement of ecabet sodium to conventional triple therapy showed good results in Asia. The Aim of this study was to ascertain the efficacy of additional ecabet sodium on conventional triple therapy for eradication of H. pylori. METHODS: We reviewed the cases of 111 patients (Group A) with H. pylori infection who received ecabet sodium with triple therapy (20 mg of rabeprazole, 1 g of amoxicillin, 500 mg of clarithromycin and 1 g of ecabet sodium, twice daily for 7 days). Another 186 patients (Group B) received PPI-based triple therapy (same as the above, except without the ecabet sodium). Eradication was evaluated 4 weeks later after completion of treatment by 13C-UBT. RESULTS: Eradication rates were 74.8% (83/111) in group A and 70.4% (131/186) in group B by intention-to-treat analysis (p=0.420), and 75.2% (82/109) in group A and 70.7% (128/181) in group B by per protocol analysis (p=0.405). CONCLUSIONS: The addition of ecabet sodium to conventional triple therapy did not increase the eradication rate of H. pylori in this study. These findings imply that ecabet sodium as an additional agent cannot overcome antibiotic resistance, which is the most important cause of failure of triple therapy.

The effects of ecabet sodium on nuclear factor-kappa B activation and chemokine gene expression in Helicobacter pylori-infected human gastric epithelial cells / 대한내과학회지

BACKGROUND: Helicobacter pylori stimulates nuclear factor-kappa B (NF-kappa B) activation and chemokine expression of gastric epithelial cells. Although ecabet sodium (ecabet), a locally acting anti-ulcer drug, is known to have an anti-H. pylori activity, there is little known how ecabet acts anti-inflammatory effects in gastric epithelial cells infected with H. pylori. We investigated the effects of ecabet on chemokine gene expression and NF-kappa B activation of human gastric epithelial cells infected with H. pylori. METHODS: After the infection of Hs746T and MKN-45 gastric epithelial cell lines with cagA+cytotoxin+ H. pylori in the presence of ecabet, mRNA expression of chemokine such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) was assessed by quantitative RT-PCR, and chemokine secretion was measured by ELISA. NF-kappa B signals were assayed by electrophoretic mobility shift assay. The activation of NF-kappa B and IL-8 reporter genes was measured by luciferase assay. RESULTS: The treatment of ecabet (5 microgram/mL) decreased the transcription and secretion of chemokine IL-8 and MCP-1 from the gastric epithelial cells infected with H. pylori in a dose-dependent manner. In addition, ecabet inhibited NF-kappa B activation of gastric epithelial cells induced by H. pylori infection. Moreover, the inhibited NF-kappa B signal by ecabet was comprised of heterodimers of p65/p50 predominantly. CONCLUSION: These results suggest that ecabet can inhibit H. pylori-induced IL-8 and MCP-1 gene transcription via suppression of NF-kappa B signal.