Rabeprazole Research Articles

Curative effect of teprenone capsule combined with quadruple therapy in the treatment of chronic atrophic gastritis

Objective To analyze the curative effect of teprenone capsule combined with quadruple therapy in the treatment of chronic atrophic gastritis. Methods From June 2013 to June 2017, one hundred and fifty patients with chronic atrophic gastritis admitted to the First Hospital of Ninghai County were retrospectively selected.According to different treatment schemes, they were divided into control group and observation group, with 75 patients in each group.The control group was treated with routine quadruple therapy, and the observation group was treated with teprenone capsule combined with quadruple therapy.The effective rate of the two groups was compared. Results The total effective rate of the observation group was 97.33%, which was higher than 85.33% of the control group, the difference between the two groups was statistically significant(χ2=3.197, P<0.05). After treatment, the levels of interleukin-8 and tumor necrosis factor-alpha in the observation group were (7.04±1.03)ng/L, (41.02±1.72)ng/L, respectively, which in the control group were (10.81±1.63)ng/L, (57.35±2.95)ng/L, respectively, the differences between the two groups were statistically significant (t=6.028, 7.281, all P<0.05). The gastric mucosa score and the gastrin concentration in the observation group were (1.13±0.32)points, (8.97±2.33)pmol/L, respectively, which in the control group were (1.82±0.61)points, (5.36±1.52)pmol/L, respectively, the differences between the two groups were statistically significant(t=5.661, 6.024, all P<0.05). Conclusion Teprenone capsule combined with quadruple therapy can improve the clinical efficacy and reduce the degree of inflammation in patients with chronic atrophic gastritis, which is worthy of clinical application. Key words: Gastritis, atrophic; Teprenone; Rabeprazole; Tinidazole; Claricid; Colloidal bismuth pectin; Interleukin-8; Tumor necrosis factor-alpha

Continuation of low-dose aspirin combined with rabeprazole on healing of peptic ulcer bleeding

Objective To investigate the effect of low-dose aspirin combined with rabeprazole on the healing of peptic ulcer after hemostasis with aspirin-related peptic ulcer bleeding, and to explore the independent factors associated with ulcer healing failure. Methods A total of 138 patients with acute upper gastrointestinal hemorrhage in the Department of Gastroenterology of the Second Affiliated Hospital of Fujian Medical University from June 2016 to June 2018 were enrolled.The clinical data of 138 patients with upper gastrointestinal ulcer bleeding caused by aspirin were analyzed.The patients were randomly divided into two groups.Aspirin group (n=68) received aspirin 100 mg/d plus rabeprazole 80 mg/d, while the placebo group (n=70) received rabeprazole 80 mg/d plus placebo.The patients were treated for 8 weeks.Subjects with H. pylori infection were treated with standard quadruple therapy.Follow-up endoscopy was performed at the end of 8 weeks.The primary endpoint was the healing of peptic ulcers. Results The ulcer healing rate was 79.4%(54/68) in the aspirin group and 84.3%(59/70) in the placebo group.There was no statistically significant difference between the two groups(χ2=0.552, P>0.05). There were 5 cases of ulcer bleeding in aspirin group and placebo group.The rehaemorrhage rate was 7.4%(5/68) and 7.1%(5/70), respectively.There was no statistically significant difference between the two groups(χ2=0.002, P>0.05). Among the factors affecting the healing of aspirin-associated peptic ulcer, the healing rate was significantly associated with steroid use during treatment (χ2=6.135, P=0.041) and smoking status(χ2=5.616, P=0.018). Other factors, including age, hypertension, diabetes, alcohol history, history of previous ulcer bleeding, initial Helicobacter pylori status, and ulcer location did not affect ulcer healing. Conclusion After aspirin-associated peptic ulcer bleeding, continued low-dose aspirin plus rabeprazole did not affect the healing of peptic ulcers, and the use of steroids and smoking status are independent risk factors for ulcer healing. Key words: Dose-response relationship, drug; Aspirin; Nonsteroidal antiinflammatory drugs; Rabeprazole; Drug therapy, combination; Peptic ulcer hemorrhage; Peptic ulcer; Risk factors

Dual Component Tablets for the Treatment of Gastroesophageal Reflux Disease

Background and Objective: Gastroesophageal reflux disease (GERD) is one of the most common GIT disorders in which reflux of the GIT contents occurs into the esophagus. The present study is focused on developing a dual component tablet containing a sustained release floating layer of Baclofen and delayed release microspheres of Rabeprazole sodium for the effective treatment of Gastroesophageal Reflux Disease (GERD). &lt;/P&gt;&lt;P&gt; Methods:Dual component tablets have been developed to achieve a controlled delivery of two different drugs. Microspheres were prepared by the emulsion solvent evaporation method using different ratios of Eudragit S100 and Rabeprazole sodium (3:1, 6:1, 9:1 and 12:1) and optimized using various parameters. Baclofen floating tablets were prepared by the wet granulation method by using different polymers like sodium alginate (S1), pectin (S2) and guar gum (S3) and characterized for their floating properties and in-vitro drug release study. &lt;/P&gt;&lt;P&gt; Results: The cumulative percentage drug release after 9 hrs was found to be in the range of 46.18 to 65.78% for different microsphere formulations. The result showed that, as the amount of polymer increased, the particle size and % yield were also increased, and drug release and entrapment efficiency were decreased. Among all the formulations, M2 was considered as the best because it showed highest entrapment efficiency. Among baclofen floating tablet formulations, S1 was resulted as optimized formulation because it sustained the drug release up to 8 hrs and showed 64.82±0.82% drug release. Conclusion: From the above optimized formulations bilayer tablets containing floating layer of Baclofen and Rabeprazole sodium loaded microspheres layer were prepared by single-punch tablet machine and evaluated for the weight variation, hardness, thickness, diameter, friability, floating time etc. The results of the study showed that all parameters were within pharmacopoeial limits.

Stereoselective pharmacokinetics of (R)-(+)- and (S)-(-)-rabeprazole in human using chiral LC-MS/MS after administration of rabeprazole sodium enteric-coated tablet.

Rabeprazole is an effective proton pump inhibitor to treat acid-related diseases. To achieve the simultaneous determination of rabeprazole enantiomers in human plasma, a chiral LC-MS/MS method was developed and validated. Acetonitrile including 0.1% ammonium were used as protein precipitating agent. Analytes were separated within 8minutes on a Chiralpak IC column (4.6mm×150mm, 5μm). The mobile phase was 10mM ammonium acetate including 0.2% acetic acid-acetonitrile (35:65, v/v). An API 4000 mass spectrometer was used as detector for the analysis, and the multiple reactions monitoring transitions of m/z 360.1→242.2 and 346.1→198.1 were opted for quantifying rabeprazole enantiomers and internal standard. Matrix effects were not apparent for each enantiomer and internal standard (esomeprazole), the calibration curves were linear over the concentration of 0.500 to 400ng·mL-1 , the intra-run precisions were below 5.4%, the inter-run precisions were below 9.9%, and the accuracy was between -9.2% and 9.3%. There was no chiral inversion observed during sample storage, preparation procedure, and analysis, demonstrating that analytes were stable in this study. This method was applied to the stereoselective pharmacokinetic study of (R)-(+)- and (S)-(-)-rabeprazole after oral administration of 10-mg rabeprazole sodium enteric-coated tablet in healthy Chinese subjects.

减少雷贝拉唑钠输液中不溶性微粒的配制方法优化

减少雷贝拉唑钠输液中不溶性微粒的配制方法优化

Clinical effect of mosapride combined with rabeprazole in the treatment of elderly patients with reflux esophagitis

Objective To explore the clinical effect of mosapride combined with rabeprazole in the treatment of elderly patients with reflux esophagitis. Methods Clinical data of 126 elderly patients with reflux esophagitis were retrospectively studied.64 cases in the study group were treated with mosapride combined with rabeprazole, 62 cases in the control group were treated with mosapride combined with omeprazole.The clinical effects between the two groups were compared. Results Before treatment, there were no statistically significant differences in the scores of pain of patients with heartburn, acid reflux and chest between the two groups(t=0.512, 0.181, 0.228, all P>0.05). After treatment, the symptom scores of the study group were significantly lower than those of the control group(t=3.689, 4.892, 5.571, all P<0.01). The clinical symptoms and esophageal mucosal total effective rate in the study group were significantly higher than those in the control group(96.88% vs.87.10%, 93.75% vs.80.65%, χ2=4.121, 4.479, all P<0.05). The scores of quality of life scale of the study group were significantly higher than those of the control group in cognitive function, mental function, physical function and social function(t=4.920, 6.853, 4.153, 6.163, all P<0.01). Conclusion Mosapride combined with rabeprazole in the treatment of elderly patients with reflux esophagitis can effectively relieve symptoms of heartburn, acid reflux and chest pain, help patients with mucosa recovery as soon as possible, improve the quality of life of patients, and it is worthy of clinical application. Key words: Esophagitis, peptic; Mosapride; Rabeprazole; Quality of life

Development, In Vitro and In Vivo Evaluation of Hydrogel Based System of Carboxymethyl Arabinoxylan for Controlled Delivery of Rabeprazole Sodium

ABSTRACTPresent study deals with development of polymeric systems for rabeprazole sodium to accomplish a lingering therapeutic outcome. Carboxymethyl arabinoxylan exhibited variety of ideal characteristics for polymeric drug carrier. Free radical polymerization was successfully employed to prepare pH responsive polymeric network of carboxymethyl arabinoxylan with acrylic acid. FTIR, SEM, thermogravimetric analysis and X-ray diffraction verified the graft copolymerization. Graft copolymers revealed highly pH responsive swelling, consequently drug release at intestinal pH. In vivo evaluation indicated improvement in relative bioavailability by exhibiting increase in Cmax of polymeric system and same oral dose of rabeprazole sodium were 103.71 ± 16.081 and 61.263 ± 5.37 ng/mL, respectively.

Vonoprazan, a Novel Potassium-Competitive Acid Blocker, Should Be Used for the Helicobacter pylori Eradication Therapy as First Choice: A Large Sample Study of Vonoprazan in Real World Compared with Our Randomized Control Trial Using Second-Generation Proton Pump Inhibitors for Helicobacter pylori Eradication Therapy

Background/Aims: Phase III study demonstrated that vonoprazan-based Helicobacter pylori eradication therapy achieved higher eradication rate compared with lansoprazole. However, there is no study that evaluated the efficacy of vonoprazan in a large sample in real world. We investigated the eradication rate and safety of vonoprazan-based eradication therapy compared with our randomized control trial using second-generation proton pump inhibitor (PPIs). Methods: (First study) A total of 147 patients who have H. pylori infection were randomly assigned to receive either, esomeprazole (EPZ) group and rabeprazole (RPZ) group. (Second study) 1,688 patients who have H. pylori infection underwent primary eradication with triple therapy involving vonoprazan. In both studies, triple therapy with amoxicillin, clarithromycin, and PPI or vonoprazan was performed, and eradication effect was assessed by an urea breath test. Results: (First study) Eradication rate was 77.5% in the EPZ group and 68.4% in the RPZ group; no significant difference was observed between the 2 groups. (Second study) The successful primary eradication rate was 90.8%. There was no severe adverse effect. Conclusions: The eradication rate of vonoprazan-based triple therapy was remarkably higher compared with second-generation PPIs-based triple therapy in real world. Vonoprazan is very likely to become the first option for future eradication therapy.

Efficacy and Safety Profile of Z-215 (Azeloprazole Sodium), a Proton Pump Inhibitor, Compared with Rabeprazole Sodium in Patients with Reflux Esophagitis: A Phase II, Multicenter, Randomized, Double-Blind, Comparative Study

BackgroundThe metabolism of many proton pump inhibitors is influenced by CYP2C19 genotype, which is a limitation of their use. ObjectivesTo determine the efficacy and safety profile of Z-215 (azeloprazole sodium) as initial treatment for reflux esophagitis (RE), dose response, and optimal dose compared with rabeprazole sodium (RPZ). MethodsWe conducted an exploratory, multicenter, randomized, double-blind, parallel-group study in Japan. Patients with RE aged ≥20 years were enrolled and randomly assigned to receive 10, 20, or 40 mg Z-215 or 10 mg RPZ (1:1:1:1), and orally administered the respective drug for 8 weeks. The primary efficacy end point was the endoscopic healing rate after 8 weeks of treatment (at Week 8). We also assessed the effects of CYP2C19 genotype. Safety end points were the incidence of adverse events and adverse drug reactions. ResultsFive hundred three patients received the study drugs (10 mg Z-215: 125 patients, 20 mg Z-215: 126 patients, 40 mg Z-215: 126 patients, and 10 mg RPZ: 126 patients). The endoscopic healing rate at Week 8 was above 95% in all groups (10 mg Z-215: 95.2%, 20 mg Z-215: 96.8%, 40 mg Z-215: 95.2%, and 10 mg RPZ: 96.8%). The endoscopic healing rate and serum gastrin levels of the Z-215 groups were not influenced by CYP2C19 genotype. In patients with Grade C/D, the endoscopic healing rate at Week 4 was slightly higher in the 40-mg Z-215 group compared with the other groups. Incidences of adverse events/adverse drug reactions did not markedly differ between the Z-215 and 10-mg RPZ groups. ConclusionsZ-215 was as effective and well tolerated as 10 mg RPZ in the treatment of RE in this selected population. CYP2C19 genotype status may not influence the efficacy and safety of Z-215. There were no clear dose–response effects between Z-215 doses in the endoscopic healing of RE. These findings suggest that Z-215 may be 1 option for the initial treatment of RE. ClinicalTrials.gov identifier: NCT 02463643.

Development of Duodenal Ulcers due to the Discontinuation of Proton Pump Inhibitors After the Induction of Sofosbuvir Plus Ledipasvir Therapy: A Report of Two Cases

Sofosbuvir plus ledipasvir (SOF-LDV) combination therapy is a promising therapy for post-transplant hepatitis C virus (HCV) reinfection. It is known that gastric pH elevation induces lower absorption of ledipasvir; therefore, the use of proton pump inhibitors (PPIs) should be considered regarding dose reduction after SOF-LDV therapy induction. Here, we report two patients who developed duodenal ulcers due to the discontinuation of PPIs after the induction of SOF-LDV therapy for post-transplant HCV reinfection. The first patient was a 71-year-old man who had undergone living donor liver transplantation due to HCV-related liver cirrhosis. Lansoprazole, 30 mg daily, was discontinued upon SOF-LDV therapy induction. Seven days after SOF-LDV therapy induction, gastrointestinal endoscopy revealed the presence of a duodenal ulcer. The second patient was a 54-year-old man who had undergone living donor liver transplantation due to HCV-related end-stage liver disease. Similar to the first patient, rabeprazole sodium was discontinued upon the induction of SOF-LDV therapy. Eighteen days after SOF-LDV therapy induction, gastrointestinal endoscopy revealed the presence of a duodenal ulcer. In both cases, these duodenal ulcers improved after the resumption of the administration of PPIs, and a sustained virologic response at 12 weeks was achieved by SOF-LDV therapy with PPI use. Thus, PPI use should be continued consistently during SOF-LDV therapy for post-transplant HCV reinfection.

Pharmacokinetics and Pharmacodynamics of Azeloprazole Sodium, a Novel Proton Pump Inhibitor, in Healthy Japanese Volunteers.

The pharmacokinetics (PK) and pharmacodynamics (PD) of proton pump inhibitors differ among cytochrome P450 (CYP) 2C19 genotypes. Therefore, we developed azeloprazole sodium (Z-215), a novel proton pump inhibitor, whose metabolism is not affected by CYP2C19 activity in vitro. However, the PK and PD of azeloprazole sodium have not been evaluated in Japanese subjects. We conducted an open-label, crossover study in healthy Japanese male volunteers to evaluate the plasma concentration and intragastric pH with respect to CYP2C19 genotype after repeated administration of 10, 20, and 40mg azeloprazole sodium and 10 and 20 mg rabeprazole sodium (rabeprazole). The plasma concentration profile of azeloprazole sodium was similar among genotypes, whereas that of rabeprazole differed. The 24-hour intragastric pH≥4 holding time ratio (pH≥4 HTR) of azeloprazole sodium was similar among genotypes. The pH≥4 HTR was 52.5%-60.3%, 55.1%-65.8%, and 69.4%-77.1% after administration of 10, 20, and 40mg azeloprazole sodium, respectively, and 59.2%-72.3% and 64.4%-91.2% after administration of 10 and 20mg rabeprazole, respectively, on the fifth day of dosing. The maximum plasma concentration (Cmax ), area under the plasma concentration-time curve (AUC), and pH≥4 HTR of azeloprazole sodium were proportional to dose. The Cmax , AUC, and pH≥4 HTR on day 5 were slightly higher following administration of 20mg azeloprazole sodium before comparison with after a meal. No serious adverse events were observed. These results suggest that azeloprazole sodium is useful for treating gastroesophageal reflux disease in all CYP2C19 genotypes.

METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF LEVOSULPIRIDE AND RABEPRAZOLE SODIUM: A NEW ANALYTICAL Q-ABSORBANCE RATIO APPROACH

Objective: The aim of the study was to develop a precise, accurate, and rapid ultraviolet spectrophotometric method for simultaneous estimation of levosulpiride (LEVO) and rabeprazole sodium (RBS) in the binary mixture and to validate the method as per ICH guidelines.Method: Estimation of LEVO and RBS was performed by Q-absorbance method. Analysis was performed using the ratio of absorbance at two selected wavelengths, one at iso-absorptive point and other is the absorbance maxima of any one of the components. Single scan spectrum and the overlain spectrum conclude that absorbance maxima of LEVO and RBS are 228 and 291.8 nm, respectively, with a coinciding iso-absorptive point at 255 nm. Method uses a ratio of absorbance for assay at 255 and the second wavelength is 291.8 nm, λmax for RBS. It is also applicable at 228 nm, as the second wavelength.Results: Linearity of LEVO and RBS was found to be 25-125 and 4-36 μg/ml, respectively. The accuracy of the LEVO and RBS was found 99.26% and 99.51%, respectively and Sandell’s sensitivity ranged between 0.0238 and 0.594 μg/cm2. Assay of LEVO (75 mg) and RBS (20 mg) in capsule dosage form was found 99.5% and 98.69% w/w, respectively.Conclusions: The developed method for the estimation of LEVO and RBS in binary mixture were found to be simple, accurate, robust, and reproducible. No interference of excipients and the degraded product was found during the estimation. Therefore, the method can be successfully applied for routine quality control analysis.RBS) in the binary mixture and to validate the method as per ICH guidelines.Method: Estimation of LEVO and RBS was performed by Q-absorbance method. Analysis was performed using the ratio of absorbance at two selected wavelengths, one at iso-absorptive point and other is the absorbance maxima of any one of the components. Single scan spectrum and the overlain spectrum conclude that absorbance maxima of LEVO and RBS are 228 and 291.8 nm respectively with a coinciding iso-absorptive point at 255 nm. Method uses ratio of absorbance for assay at 255 and the second wavelength is 291.8 nm, λmax for RBS. It is also applicable at 228 nm, as the second wavelength.Results: Linearity of LEVO and RBS were found to be 25-125and 4-36 μg/ml respectively. Accuracy of the LEVO and RBS was found 99.26 and 99.51% respectively and Sandell’s sensitivity ranged between 0.0238 and 0.594 𝜇g/cm2. Assay of LEVO (75 mg) and RBS (20 mg) in capsule dosage form was found 99.5 and 98.69% w/w respectively.Conclusions: The developed method for the estimation of LEVO and RBS in binary mixture were found to be simple, accurate, robust and reproducible. No interference of excipients and the degraded product were found during the estimation. Therefore the method can be successfully applied for routine quality control analysis.

A rapid Fourier transform infrared spectroscopic method for analysis of certain proton pump inhibitors in binary and ternary mixtures

A simple and non-destructive FTIR method was used to determine certain proton pump inhibitors (PPIs) in binary and ternary mixtures. Proton pump inhibitors (PPIs); omeprazole (OMZ), esomeprazole (EZM), lansoprazole (LAN), pantoprazole sodium (PAN sodium) and rabeprazole sodium (RAB sodium) in binary mixture with domperidone (DOM) and ternary mixture of OMZ, clarithromycin (CLM) and tinidazole (TNZ) were determined in the solid-state by FTIR spectroscopy for the first time. The method was validated according to ICH-guidelines where linearity was ranged from 20 to 850μg/g and 20–360μg/g for PPIs and DOM, respectively in binary mixtures and 10–400, 100–8000 and 150–14,000μg/g for OMZ, CLM and TNZ, respectively. Limits of detection were found to be 6–100 and 9–100μg/g for PPIs and DOM, respectively and 4, 40 and 50μg/g for OMZ, CLM and TNZ, respectively. The method was applied successfully for determination of the cited drugs in their respective pharmaceutical dosage forms.

Effect of cytochrome P450 2C19 genotypic polymorphism on treatment efficacy for gastroesophageal reflux disease by rabeprazole

Objective To investigate whether the effect of rabeprazole in treating gastroesophageal reflux disease is related to CYP2C19 gene polymorphisms. Methods 278 patients with gastroesophageal reflux disease confirmed by endoscopy and proton-pump inhibitor testing were enrolled in this study, including non erosive reflux disease (NERD) in 122 cases, the reflux esophagitis (RE) in 98 cases and Barrett esophagus in 58 cases.They were treated with rabeprazole for 8 weeks.GerdQ scores before and after the treatment were completed, endoscopy was performed again in patients with RE after treatment.The blood CYP2C19 genotyping was detected by matrix assisted laser desorption ionization time of flight mass spectrum(MALDI-TOF-MS). Results According to the genotype of CYP2C19, they were divided into extensive metabolizers, intermediate metabolizers and poor metabolizers, accounted for 39.57%, 42.45% and 17.98%, respectively.There was no significant difference in GerdQ scores of three groups before treatment, and also had no significant difference after 8 weeks treatment, but in each subgroup GerdQ scores after treatment was decreased significantly than before treatment.The total effective rate of 98 patients with RE by endoscopy was 86.73%, but there was no significant difference in total effective rate of the three groups after treatment. Conclusion Rabeprazole is effective in the treatment of gastroesophageal reflux disease.Moreover, rabeprazole is less affected by CYP2C19 genotype and therefore its curative effect is more stable. Key words: Gtochrome P-450 enzyme system; Gastroesophageal reflux; Rabeprazole

Synthesis and Characterization of Cu(II), Zn(II), Cd(II) and Hg(II) Complexes of Rabeprazole

Rabeprazole (RPZH) (available as rabeprazole sodium, RPZNa) is a proton pump inhibitor (PPI), widely used for the treatment of acid-related diseases in the stomach and duodenum. It is a weak base with pKa= 4.9 and show a strong ability to form complexes with transition and nontransition metal ions. Its complexes with Cu(II), Zn(II), Cd(II) and Hg(II) have been synthesized and characterized by solubility, melting point, metal content estimation, IR and UV-Visible spectral analysis, magnetic measurement, thermogravimetric analysis, differential scanning calorimetry and X-ray powder diffraction studies. On the basis of metal contents, the complexes have been formulated as [Cu(RPZ)(H2O)Cl], [Zn(RPZ)2], [Cd(RPZ)2].2H2O and [Hg(RPZ)2].H2O. Rabeprazole sodium (RPZNa) loses Na+ ion in solution yielding a monoanionic RPZ that behaves as a bidentate ligand and coordinates through C-N- and S=O groups with the divalent metal ion. Tetrahedral geometry of all complexes is proposed. Zn(II), Cd(II) and Hg(II) complexes have 1:2 metal to ligand stoichiometry while Cu(II) complex possesses ligand to metal ratio of 1:1. Cu(II) and Zn(II) complexes have also been screened for their antibacterial and antifungal activities against several bacteria and fungi.&#x0D; Dhaka Univ. J. Sci. 65(2): 157-162, 2017 (July)

Repurposing of Proton Pump Inhibitors as first identified small molecule inhibitors of endo-β-N-acetylglucosaminidase (ENGase) for the treatment of NGLY1 deficiency, a rare genetic disease

N-Glycanase deficiency, or NGLY1 deficiency, is an extremely rare human genetic disease. N-Glycanase, encoded by the gene NGLY1, is an important enzyme involved in protein deglycosylation of misfolded proteins. Deglycosylation of misfolded proteins precedes the endoplasmic reticulum (ER)-associated degradation (ERAD) process. NGLY1 patients produce little or no N-glycanase (Ngly1), and the symptoms include global developmental delay, frequent seizures, complex hyperkinetic movement disorder, difficulty in swallowing/aspiration, liver dysfunction, and a lack of tears. Unfortunately, there has not been any therapeutic option available for this rare disease so far. Recently, a proposed molecular mechanism for NGLY1 deficiency suggested that endo-β-N-acetylglucosaminidase (ENGase) inhibitors may be promising therapeutics for NGLY1 patients. Herein, we performed structure-based virtual screening utilizing FDA-approved drug database on this ENGase target to enable repurposing of existing drugs. Several Proton Pump Inhibitors (PPIs), a series of substituted 1H-benzo [d] imidazole, and 1H-imidazo [4,5-b] pyridines, among other scaffolds, have been identified as potent ENGase inhibitors. An electrophoretic mobility shift assay was employed to assess the inhibition of ENGase activity by these PPIs. Our efforts led to the discovery of Rabeprazole Sodium as the most promising hit with an IC50 of 4.47±0.44μM. This is the first report that describes the discovery of small molecule ENGase inhibitors, which can potentially be used for the treatment of human NGLY1 deficiency.

A New and Cost Effective Approach for Simultaneous Voltammetric Analysis of two Related Benzimidazole Drugs and their Determination in Biological Fluids

AbstractA polymerized film of eriochrome black T (EBT) was prepared on the surface of pencil graphite electrode in alkaline solution by cyclic voltammetry. The redox response of the poly (EBT) film at the electrode appeared in a couple of redox peak in 0.1 M sodium hydroxide. The poly (EBT) film‐coated electrode exhibited excellent electrocatalytic activity towards the oxidation of rabeprazole sodium (RAB sodium) and domperidone (DOM) in Britton‐Robinson buffer (pH 4.0). The polymer film modified electrode conspicuously enhanced the redox currents of the cited mixture and could sensitively and separately determine them. Both cyclic voltammetry (CV) and square wave adsorptive stripping voltammetric (SWAdSV) methods were utilized to determine this mixture. The linearity of CV ranged from 4.1‐120 μM and 5.2‐90 μM for RAB sodium and DOM, respectively while SWAdSV was 7.5‐80×10−7M and 5–70×10−7M for RAB sodium and DOM, respectively. With good selectivity and sensitivity, the present method provides a simple method for selective detection of RAB sodium and DOM binary mixture in synthetic mixtures and biological fluids.

A multicenter randomized trial comparing rabeprazole and itopride in patients with functional dyspepsia in Japan: the NAGOYA study.

The aims of this study were to compare the therapeutic effects of a proton pump inhibitor (PPI), rabeprazole (RPZ), and a prokinetic agent, itopride (ITO), and to investigate the role of PPI in the treatment strategy for Japanese functional dyspepsia (FD) patients. We randomly assigned 134 patients diagnosed by Rome III criteria to 4 weeks treatment with RPZ 10 mg/day (n = 69) or ITO 150 mg/day (n = 65). Dyspeptic symptoms were evaluated using FD scores at baseline and after 1, 2 and 4 weeks of treatment. We also divided subjects into predominantly epigastric pain syndrome (EPS) or postprandial distress syndrome (PDS), and evaluated the efficacy of RPZ and ITO respectively. RPZ showed a significant decrease in the Rate of Change (RC) in FD score within 1 week, which was maintained until after 4 weeks, with RPZ a significant effect compared with ITO at all evaluation points. In addition, RPZ showed a significant decrease in FD score in subjects with both EPS and PDS, whereas a significant decrease in the RC with ITO was only shown in those with predominant PDS. Acid-suppressive therapy with RPZ is useful for PDS as well EPS in Japanese FD patients (UMIN Clinical Trials Registry number: UMIN 000013962).

Randomized Trial Comparing Esomeprazole and Rabeprazole in First-line Eradication Therapy for Helicobacter pylori Infection based on the Serum Levels of Pepsinogens.

Objective CYP2C19 metabolic activity influences the efficacy of Helicobacter pylori eradication therapies comprising PPIs. Rabeprazole (RPZ) and esomeprazole (EPZ) are PPIs not extensively metabolized by CYP2C19. The aim of this study was to elucidate whether or not first-line triple therapies using RPZ or EPZ are equally effective in Japanese patients with different CYP2C19 genotypes. Methods Two-hundred patients infected with H. pylori were randomized to receive one of the following regimens: amoxicillin (750 mg), clarithromycin (200 mg), and either esomeprazole (20 mg) (EAC group) or rabeprazole (10 mg) (RAC group), twice a day for one week. The CYP2C19 polymorphisms were determined by polymerase chain reaction and the serum level of pepsinogens was measured. Results The eradication rates of the EAC and RAC regimens were 79.8% (95% confidential interval: 71.7-89.0%) and 74.7% (66.0-83.4%), respectively, in a per protocol (PP) analysis (p=0.488). The eradication rates of the EAC and RAC regimens were not significantly different between patients with the homo EM genotype (p=0.999) or hetero IM or PM genotypes (p=0.286). A lower PG I/II ratio was associated with lower eradication rates (p=0.025). Conclusion Although the eradication rate was less than 80%, the EAC and RAC regimens were equally effective in each CYP2C19 genotype group. The PG I/II ratio was associated with the results of EAC and RAC therapy in this series of patients.

Formulation and Evaluation of Chronotherapeutic Pulsatile Drug Delivery System Containing Rabeprazole Sodium

Development and characterization of chronotherapeutic tablets of sacubitril-valsartan supramolecular complex using hupu gum and lannea gum by compression coatingRajeswari Aleti, Kolapalli Venkata Ramana Murthy