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Experimental and Therapeutic Medicine Dec 2014The aim of this study was to determine the transport and distribution characteristics of levofloxacin in the rat stomach and investigate the effects of combination...
The aim of this study was to determine the transport and distribution characteristics of levofloxacin in the rat stomach and investigate the effects of combination treatment with rabeprazole. A total of 160 Wistar rats were randomly divided into four treatment groups: 50 mg/kg levofloxacin, 100 mg/kg levofloxacin, 50 mg/kg levofloxacin + rabeprazole and 100 mg/kg levofloxacin + rabeprazole. For two hours after intravenous administration, serum, gastric juice and stomach mucosa samples were collected at 15-min intervals, and the levofloxacin concentrations in all the samples were measured to determine the transport and distribution characteristics of levofloxacin in the rat stomach. In the 50 mg/kg levofloxacin and the 100 mg/kg levofloxacin groups, the drug concentration in the gastric juice gradually exceeded the serum concentration within 45-60 min of administration (P<0.05) and the drug concentrations in the gastric body and antrum were higher than those in the serum and the forestomach (P<0.05). At 15-30 min after administration, the drug concentrations in the gastric juice in the 50 mg/kg levofloxacin + rabeprazole and the 100 mg/kg levofloxacin + rabeprazole groups gradually exceeded the serum concentration (P<0.05). However, the levofloxacin concentration in the gastric body and in the antrum did not significantly differ between the two groups (P>0.05). The levofloxacin concentrations in each stomach region in the groups also treated with rabeprazole were higher than those treated with levofloxacin alone, but the differences were not significant. The levofloxacin transport fractions in the stomach in the 50 mg/kg levofloxacin, 100 mg/kg levofloxacin, 50 mg/kg levofloxacin + rabeprazole and 100 mg/kg levofloxacin + rabeprazole groups were 2.36, 2.52, 2.42 and 2.55, respectively, and no significant difference was identified. Levofloxacin may be actively transported in the rat stomach. The levofloxacin concentration in the gastric antrum exceeded that in the forestomach, and the local concentration increased with increasing dosage. Combining a proton pump inhibitor with levofloxacin has little effect on the concentration and distribution of levofloxacin in the stomach within 2 h.
PubMed: 25371749
DOI: 10.3892/etm.2014.2031 -
Biochemical Pharmacology Jun 2021The dysregulation of glycolysis leads to serials of disease. Rabeprazole is a representative of proton pump inhibitors and widely used in anti-ulcer treatment. However,...
The dysregulation of glycolysis leads to serials of disease. Rabeprazole is a representative of proton pump inhibitors and widely used in anti-ulcer treatment. However, the function of Rabeprazole on glycolysis in gastric epithelial cells remained to be identified. In this study, 30(Helicobacter pylori)H. pylori-negative cases and 26H. pylori-positive cases treated with Rabeprazole were recruited. The qPCR and Western blotting results showed that Rabeprazole suppressed cell proliferation by inhibition of HK2-mediated glycolysis in BGC823 cells, leading to decrease glucose uptake and lactate production in a dose-dependent way. Furthermore, the phosphorylation of signal transducer and activator of transcription 3 (STAT3) was drastically reduced in response to Rabeprazole stimulation, leading to attenuate STAT3 nuclear translocation. Luciferase and Chromatin immunoprecipitation (ChIP) analysis showed that Rabeprazole treatment led to a significant inhibition of the binding of STAT3 to the promoter of the HK2 gene, repressing transcriptional activation of HK2. Moreover, the ectopic expression of STAT3 in BGC823 cells resulted in recovery of HK2 transactivation and cell proliferation in Rabeprazole-treated cells. Most importantly, HK2 expression was significantly increased in H. pylori-infected gastric mucosa. These findings suggested that Rabeprazole inhibited cell proliferation by targeting STAT3/HK2 signaling-mediated glucose metabolism in gastric epithelial cells. Therefore, targeting HK2 is an alternative strategy in improving the treatment of patients with H. pylori infection.
Topics: Anti-Ulcer Agents; Cell Line; Cell Proliferation; Child; Drug Delivery Systems; Epithelial Cells; Female; Gastric Mucosa; Glycolysis; Humans; Male; Rabeprazole; STAT3 Transcription Factor
PubMed: 33744226
DOI: 10.1016/j.bcp.2021.114525 -
Alimentary Pharmacology & Therapeutics Mar 2002Integrated gastric and oesophageal acidity can be calculated from measurements of gastric and oesophageal pH and used to quantify gastric and oesophageal acidity over... (Clinical Trial)
Clinical Trial
BACKGROUND
Integrated gastric and oesophageal acidity can be calculated from measurements of gastric and oesophageal pH and used to quantify gastric and oesophageal acidity over time. Rabeprazole is a new proton pump inhibitor that is effective in treating gastro-oesophageal reflux disease (GERD).
AIM
To use measurement of integrated gastric and oesophageal acidity to determine the onset, duration and overall effect of rabeprazole in subjects with GERD.
METHODS
Subjects with GERD were required to have oesophageal pH less-than-or-equal 4 for at least 10% of a 24-h recording. Effects of 20 mg rabeprazole on 24-h gastric and oesophageal pH were measured on days 1 and 7 of dosing. Integrated gastric and oesophageal acidity were calculated from time-weighted average hydrogen ion concentrations at each second of the 24-h record.
RESULTS
At steady-state, 20 mg rabeprazole inhibited gastric acidity by 89% and oesophageal acidity by 95%. The first dose of rabeprazole inhibited gastric and oesophageal acidity by at least 70% of the steady-state effect. Oesophageal acidity could be divided into monophasic and biphasic patterns, and rabeprazole had different effects on oesophageal and gastric acidity in these two GERD subpopulations. The onset of action of the first dose of rabeprazole on gastric acidity was 4 h and on oesophageal acidity was 4 h in monophasic subjects and 7 h in biphasic subjects. Integrated acidity was more sensitive than time pH less-than-or-equal 4 in measuring the inhibitory actions of rabeprazole.
CONCLUSIONS
Integrated gastric and oesophageal acidity are quantitative measurements that provide useful and novel information regarding the pathophysiology of GERD as well as the impact of antisecretory agents such as rabeprazole.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Benzimidazoles; Esophagitis, Peptic; Female; Gastric Acid; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole; Rabeprazole; Treatment Outcome
PubMed: 11876698
DOI: 10.1046/j.1365-2036.2002.01158.x -
Medicine Nov 2022Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy and safety of first-line therapy, the choice of individual PPIs or vonoprazan in the treatment of EE remains controversial. This study aimed to evaluate the efficacy and safety of vonoprazan and PPIs in healing esophageal mucosal injury in patients with EE.
METHODS
Relevant databases were searched to collect randomized controlled trials of proton pump inhibitors and vonoprazan in the treatment of reflux esophagitis up to December 2021. Studies on standard-dose PPIs or vonoprazan that were published in Chinese or English and assessed healing effects in EE were included in the analysis. Stata16.0 was used to conduct a network Meta-analysis to evaluate the efficacy and safety of the treatment.
RESULTS
A total of 41 literatures were included with 11,592 enrolled patients. For the endoscopic cure rate, all the PPIs and vonoprazan significantly improve compared to Placebo; Based on the surface under the cumulative ranking curve, Ilaprazole ranked first, followed by esomeprazole, vonoprazan, pantoprazole, lansoprazole, omeprazole, rabeprazole and placebo therapy ranked the last. For the rate of adverse events, there was no significant difference among all the PPIs, vonoprazan, and placebo.
CONCLUSIONS
Ilaprazole, esomeprazole and vonoprazan have more advantages in mucosal erosion healing, there was no significant difference in the comparative safety among all interventions.
Topics: Humans; Proton Pump Inhibitors; Esomeprazole; Network Meta-Analysis; Peptic Ulcer; Rabeprazole; Esophagitis, Peptic; Abdominal Injuries
PubMed: 36451489
DOI: 10.1097/MD.0000000000031807 -
Gut and Liver Jun 2008Nocturnal reflux is a largely undiagnosed and unmanaged condition predisposing to multiple esophageal complications. We evaluated the effects of rabeprazole and...
BACKGROUND/AIMS
Nocturnal reflux is a largely undiagnosed and unmanaged condition predisposing to multiple esophageal complications. We evaluated the effects of rabeprazole and pantoprazole on nocturnal intragastric pH and gastric acid output during Day 1 of therapy following the consumption of standard meals.
METHODS
The study had a double-blinded, randomized, two-way crossover design, and involved 15 patients with a history of mild reflux. Following an overnight fast, patients were given either rabeprazole (20 mg) or pantoprazole (40 mg) prior to the first of three standard Western meals. They then underwent overnight continuous intragastric pH monitoring and gastric acid output measurement. The drug effect was analyzed using a two-treatment, two-period crossover mixed model.
RESULTS
The percentage of time during which the mean intragastric pH was greater than 4.0 and gastric acid output was less than 2.0 was higher for oral rabeprazole (p<0.05). The inhibition of acid output was greater for rabeprazole at almost all time points. Furthermore, the mean time-matched pH values differed significantly over the first 8.3 hours (p<0.05).
CONCLUSIONS
On day 1, oral rabeprazole inhibited acid output to a greater extent and for a longer period than pantoprazole, and the intragastric pH was significantly higher for rabeprazole than for pantoprazole over the first 8.3 hours.
PubMed: 20485608
DOI: 10.5009/gnl.2008.2.1.30 -
Archives of Cardiovascular Diseases Dec 2013Several studies have suggested that proton-pump inhibitors (PPIs), mostly omeprazole, interact with clopidogrel efficacy by inhibiting the formation of its active... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Several studies have suggested that proton-pump inhibitors (PPIs), mostly omeprazole, interact with clopidogrel efficacy by inhibiting the formation of its active metabolite via CYP2C19 inhibition. Whether this occurs with all PPIs is a matter of debate. As rabeprazole is a less potent CYP2C19 inhibitor than other PPIs, we studied the interaction between rabeprazole and the antiplatelet actions and pharmacokinetics of clopidogrel.
AIM
To demonstrate the non-inferiority of rabeprazole over placebo using change in platelet reactivity index (PRI; vasodilator-stimulated phosphoprotein [VASP] assay) in a predefined population of good clopidogrel responders. Omeprazole was used as the positive control.
METHODS
In this randomized three-period crossover study in healthy volunteers, 36 healthy men received clopidogrel (75 mg/day for 7 days) with placebo, omeprazole (20mg/day) or rabeprazole (20mg/day). Clopidogrel antiplatelet effects and disposition kinetics were assessed on day 7 of combination therapy. Non-inferiority threshold was predefined as an upper limit of the 90% confidence interval for the difference in change in PRI between placebo and rabeprazole of<10% in good clopidogrel responders.
RESULTS
In good clopidogrel responders (inhibition of VASP index>30%), the clopidogrel antiplatelet effect remained non-inferior to placebo during rabeprazole (difference 3.4% [-1.7; 8.5]) but not omeprazole (difference 7.5% [2.5; 12.6]) co-administration. The AUC0-24 and Cmax of active clopidogrel metabolite decreased with both omeprazole and rabeprazole, and conditions of bioequivalence were not met, except for AUC0-24 with rabeprazole.
CONCLUSIONS
Rabeprazole does not interact with clopidogrel to the same extent as omeprazole. However, under our experimental conditions and proton-pump inhibitor doses, there was no significant pharmacodynamic interaction between rabeprazole or omeprazole and clopidogrel, despite a significant decrease in the formation of clopidogrel active metabolite.
Topics: Adult; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Biotransformation; Blood Platelets; Cell Adhesion Molecules; Clopidogrel; Cross-Over Studies; Cytochrome P-450 CYP2C19; Drug Administration Schedule; Drug Interactions; Enzyme Inhibitors; Half-Life; Healthy Volunteers; Humans; Male; Metabolic Clearance Rate; Microfilament Proteins; Omeprazole; Paris; Phosphoproteins; Phosphorylation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Proton Pump Inhibitors; Rabeprazole; Ticlopidine
PubMed: 24246616
DOI: 10.1016/j.acvd.2013.09.002 -
Frontiers in Medicine 2021Proton pump inhibitors (PPIs) are validated gastric acid suppressors and have been widely used to treat patients with active duodenal ulcers. Although existing PPIs...
Mucosal Healing Effectiveness and Safety of Anaprazole, a Novel PPI, vs. Rabeprazole in Patients With Duodenal Ulcers: A Randomized Double-Blinded Multicenter Phase II Clinical Trial.
Proton pump inhibitors (PPIs) are validated gastric acid suppressors and have been widely used to treat patients with active duodenal ulcers. Although existing PPIs have shown great efficacy, many scientists are still devoted to developing more effective PPIs with better safety profile. Herein, we aimed to compare the safety and efficacy of anaprazole in duodenal mucosal healing, a novel PPI, to that of rabeprazole. In this multicenter, randomized, positive-controlled, double-blinded, parallel-group phase II clinical trial, a total of 150 qualified patients with endoscopically confirmed active duodenal ulcers were randomized (1:1:1) to receive rabeprazole 10 mg, anaprazole 20 mg or anaprazole 40 mg for 4 weeks. The ulcer healing rates after 4 weeks of treatment were compared between groups by independent central review and investigator review. In addition, symptoms and safety were evaluated. Based on the independent central review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole and 40 mg anaprazole groups were 88.0, 85.1, and 87.5%, respectively, in the FAS population and 88.9, 86.0, and 90.9%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -2.9% (95% CI, -16.5-10.7%), and -0.5% (95% CI, -13.5-12.5%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Based on the investigator review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole, and 40 mg anaprazole groups were 72.0, 70.2, and 77.1%, respectively, in the FAS population and 75.6, 72.1, and 79.5%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -1.8% (95% CI, -19.8-16.3%), and 5.1% (95% CI, -12.2-22.3%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Most patients (>90%) eventually achieved complete symptom relief. The incidence rates of adverse events were of no significant differences among the treatment groups. Potential possible better liver tolerance was observed in two anaprazole dose groups than rabeprazole 10 mg group. Both at a dosage of 20 and 40 mg daily, anaprazole, is effective with good safety profile in the treatment of active duodenal ulcers in this Phase 2 study, which allows anaprazole to be advanced to a phase III clinical trial. https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT04503629&cntry=&state=&city=&dist=, Identifier: CTR20181464, NCT04503629.
PubMed: 34336894
DOI: 10.3389/fmed.2021.690995 -
Alimentary Pharmacology & Therapeutics Aug 1999The proton pump inhibitors rabeprazole, omeprazole, lansoprazole, and pantoprazole undergo an extensive hepatic biotransformation. In the liver, they are metabolized to... (Review)
Review
The proton pump inhibitors rabeprazole, omeprazole, lansoprazole, and pantoprazole undergo an extensive hepatic biotransformation. In the liver, they are metabolized to varying degree by several cytochrome P450 (CYP) isoenzymes which are further categorized into subfamilies of related polymorphic gene products. The principal isoenzymes involved in the metabolism of proton pump inhibitors are CYP2C19 and CYP3A4. Of these two, minor mutations in CYP2C19 affect its activity in the liver and, in turn, the metabolic and pharmacokinetic profiles of the proton pump inhibitors. The metabolism of rabeprazole is less dependent on CYP2C19 and therefore is the least affected by this genetic polymorphism. Recent studies have brought to light the important role that this polymorphism plays in the therapeutic effectiveness of proton pump inhibitors during the treatment of acid-related diseases.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Anti-Ulcer Agents; Benzimidazoles; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Humans; Omeprazole; Proton Pump Inhibitors; Rabeprazole
PubMed: 10491726
DOI: 10.1046/j.1365-2036.1999.00022.x -
Gastroenterology Research and Practice 2022Peptic ulcer is a multifactorial and complex disease and affects a wide range of people worldwide. We provided a novel therapeutic approach for peptic ulcer and observed...
PURPOSE
Peptic ulcer is a multifactorial and complex disease and affects a wide range of people worldwide. We provided a novel therapeutic approach for peptic ulcer and observed its effect.
METHODS
Peptic ulcer patients were enrolled from 2016 to 2017 in Chongqing and randomly assigned to two groups: a control group that used only rabeprazole and a platelet-rich plasma (PRP) group that received a combination therapy of autologous PRP (aPRP) and rabeprazole. The therapeutic effect was assessed via the ulcer size and symptom score.
RESULTS
A total of 27 patients were included (12 patients in the control group and 15 patients in the PRP group) in this study. Our results showed that all participants have healed in 30 days, and there was no significant difference in healing time between the PRP group and the control group in different independent variables. However, regression analysis revealed that the healing time was 6.99 days shorter in the PRP group than that in the control group, and patients with higher symptom scores in the initial examination need more time to heal during treatment. Endoscopic results showed that the repaired ulcer in the PRP group was more similar to the normal gastric mucosa tissue than that the control group.
CONCLUSION
This study showed an encouraging preliminary result that aPRP has a positive result in patients with peptic ulcer and seems to be a better choice for refractory peptic ulcer treatment. Although further follow-up studies are needed to determine the duration of efficacy of aPRP, the approach will be helpful in improving the clinical treatment of peptic ulcer.
PubMed: 35873352
DOI: 10.1155/2022/7944849 -
Frontiers in Immunology 2022Behcet's disease (BD) is a chronic immune disease that involves multiple systems. As the pathogenesis of BD is not clear, and new treatments are needed, we used...
BACKGROUND
Behcet's disease (BD) is a chronic immune disease that involves multiple systems. As the pathogenesis of BD is not clear, and new treatments are needed, we used bioinformatics to identify potential drugs and validated them in mouse models.
METHODS
Behcet's disease-related target genes and proteins were screened in the PubMed and UVEOGENE databases. The biological functions and pathways of the target genes were analyzed in detail by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed by the STRING database, and hub genes were identified by the Cytoscape plug-in CytoHubba. Gene-drug interactions were identified from the DGIdb database. Experimental autoimmune uveitis (EAU) mice were used as an animal model for drug validation.
RESULTS
A total of 249 target genes and proteins with significant differences in BD were screened, and the results of functional enrichment analysis suggested that these genes and proteins were more located on the cell membrane, involved in regulating the production of cytokines and affecting the activity of cytokines. They mainly regulated "Cytokine- Cytokine receptor interaction", "Inflammatory bowel disease (IBD)" and "IL-17 signaling Pathway". In addition, 10 hub genes were obtained through PPI network construction and CytoHubba analysis, among which the top 3 hub genes were closely related to BD. The DGIdb analysis enriched seven drugs acting together on the top 3 hub genes, four of which were confirmed for the treatment of BD or its complications. There is no evidence in the research to support the results in omeprazole, rabeprazole, and celastrol. However, animal experiments showed that rabeprazole and celastrol reduced anterior chamber inflammation and retinal inflammation in EAU mice.
CONCLUSIONS
The functional analysis of genes and proteins related to BD, identification of hub genes, and validation of potential drugs provide new insights into the disease mechanism and potential for the treatment of BD.
Topics: Animals; Behcet Syndrome; Computational Biology; Cytokines; Gene Expression Profiling; Inflammation; Mice; Rabeprazole; Uveitis
PubMed: 35799784
DOI: 10.3389/fimmu.2022.895869