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Terapevticheskii Arkhiv Oct 2022To evaluate the advantages of using combined therapy of proton-pump inhibitors (PPIs) and esophagoprotector in comparison with basic therapy of PPIs for 4 weeks based on...
AIM
To evaluate the advantages of using combined therapy of proton-pump inhibitors (PPIs) and esophagoprotector in comparison with basic therapy of PPIs for 4 weeks based on the results of changes in the endoscopic picture.To compare the effectiveness of 4-week PPI therapy and 4-week combination therapy with PPI and esophagoprotector Alfasoxx (sodium hyaluronate, chondroitin sulfate, poloxomer 407) in patients with erosive esophagitis (EE) of any degree according to the Los Angeles Endoscopic Classification.
MATERIALS AND METHODS
81 patients with EE AC according to the Los Angeles endoscopic classification (1994) was enrolled in the study on the basis of the clinic of Peter the Great, Mechnikov North-Western State Medical University. By computer randomization, patients were divided into the control group 40 patients (pantoprazole 40 mg 1 time per day) and the intervention group 41 patients (pantoprazole 40 mg 1 time per day + Alfasoxx 1 sachet qid). The therapy was carried out for 4 weeks. In all patients before and after therapy, the frequency and severity of the main symptoms of gastroesophageal reflux disease (GERD) were assessed, esophagogastroduodenoscopy was performed.
RESULTS
The advantage of combination therapy over standard PPI monotherapy in patients with EE was revealed. According to the results of the control endoscopy, healing of erosions of the esophageal mucosa was observed in 39 out of 41 (95.1%) patients in the intervention group and 32 out of 39 (82.1%) in the control group. The proportion of patients who showed an improvement in the endoscopic picture before and after treatment for 4 weeks by at least 1 level according to the Los Angeles classification was significantly higher in the comparison group 41 patients (100%), while in the control group 33 patients (85%); p0.009. After treatment, the combination therapy group had a lower incidence (p0.01) and severity of heartburn (p0.01). The same results are demonstrated by combination therapy regarding the symptom belching of air: in the study group after treatment, this symptom occurred less frequently (p=0.014), its severity was significantly less than in the control group (p0.01). There was a statistically significant decrease in the need for on-demand antacid therapy in the study group.
CONCLUSION
In this study involving 81 patients with erosive GERD, the benefits of combination therapy were demonstrated. The addition of Alfasoxx medical device to PPI therapy increases the clinical and endoscopic efficacy of therapy. This positive effect is associated with the esophagoprotective properties of the drug, based on unique pharmacodynamic characteristics. Combination therapy for GERD is preferred in patients with EE. Studies have shown the expediency of using Alfasoxx in case of insufficient effectiveness of classical acid-suppressive therapy for GERD.
Topics: Humans; Proton Pump Inhibitors; Pantoprazole; Antacids; Hyaluronic Acid; Chondroitin Sulfates; Esophagitis; Gastroesophageal Reflux; Peptic Ulcer; Treatment Outcome
PubMed: 36286979
DOI: 10.26442/00403660.2022.08.201828 -
Toxicology Letters Oct 2020Proton pump inhibitors (PPIs) have wide pleiotropic action in addition to their therapeutic potential in gastroesophageal reflux diseases. Conversely, recent reports...
Proton pump inhibitors (PPIs) have wide pleiotropic action in addition to their therapeutic potential in gastroesophageal reflux diseases. Conversely, recent reports revealed a significant incidence of toxic events of PPIs including nephritis, osteoporosis, and cardiac damage. Thus, the study was designed to reconcile the deceptive contraindications. The present investigation targeted to reveal the toxic impact of sub-acute and sub-chronic administration of pantoprazole (PPZ) with different concentrations (low dose 4 mg/kg, medium-dose 8 mg/kg and high dose 16 mg/kg once a day) on normal vascular endothelium and renal tissue of rats. Vascular endothelial dysfunction (VED) was estimated by the contractility of an isolated aortic ring, nitrite/nitrate concentration, oxidative stress, and integrity of the endothelium layer. Moreover, the renal abnormalities were further confirmed by an increased level of serum creatinine, blood urea nitrogen (BUN), the incidence of microproteinuria, and structural alteration. Sub-acute administration of PPZ treatment did not produce any toxicological impact on endothelium and renal tissue. Whereas, sub-chronic administration of PPZ treatment causes moderate VED and renal dysfunction in a dose-dependent manner. Sub-chronic treatment of PPZ also influences the mitigation of NO and elevation of oxidative stress. Collecting all the evidence, it concludes that decreased nitric oxide availability and increased levels of oxidative stress may be a possible underlying mechanism of causing VED and renal abnormalities from high-dose PPZ treatment.
Topics: Administration, Oral; Animals; Aorta, Thoracic; Cytokines; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Kidney; Lipid Peroxidation; Male; Nitrates; Nitrites; Pantoprazole; Proton Pump Inhibitors; Rats; Rats, Wistar; Vasodilation
PubMed: 32763312
DOI: 10.1016/j.toxlet.2020.07.031 -
Clinical Pharmacology in Drug... Oct 2022Ripretinib is a switch control KIT kinase inhibitor approved for treatment of adults with advanced gastrointestinal stromal tumors who received prior treatment with 3 or...
Ripretinib is a switch control KIT kinase inhibitor approved for treatment of adults with advanced gastrointestinal stromal tumors who received prior treatment with 3 or more kinase inhibitors, including imatinib. Ripretinib and its active metabolite (DP-5439) are cleared mainly via cytochrome P450 enzyme 3A4/5 (CYP3A4/5), and ripretinib solubility is pH-dependent, thus the drug-drug interaction potentials of ripretinib with itraconazole (strong CYP3A inhibitor), rifampin (strong CYP3A inducer), and pantoprazole (proton pump inhibitor) were each evaluated in open-label, fixed-sequence study designs. Overall, 20 participants received ripretinib 50 mg alone and with itraconazole 200 mg once daily, 24 participants received ripretinib 100 mg alone and with rifampin 600 mg once daily, and 25 participants received ripretinib 50 mg alone and with pantoprazole 40 mg once daily. Ripretinib exposure increased with concomitant itraconazole, with geometric least-squares (LS) mean ratios of ripretinib area under the concentration-time curve from 0 to ∞ (AUC ) and maximum observed concentration (C ) of 199% and 136%. Ripretinib exposure decreased with concomitant rifampin: geometric LS mean ratios for ripretinib AUC and C were 39% and 82%. Pantoprazole coadministration had no effect on ripretinib pharmacokinetics. No unexpected safety signals occurred. No dose adjustment is required for ripretinib coadministered with gastric acid reducers and strong CYP3A inhibitors; patients also receiving strong CYP3A inhibitors should be monitored more frequently for adverse reactions. Concomitant ripretinib use with strong CYP3A inducers should be avoided. Prescribers should refer to approved labeling for specific dose recommendations with concomitant use of strong and moderate CYP3A inducers.
Topics: Adult; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Therapy, Combination; Gastric Acid; Humans; Imatinib Mesylate; Itraconazole; Naphthyridines; Pantoprazole; Protein Kinase Inhibitors; Proton Pump Inhibitors; Rifampin; Urea
PubMed: 35560823
DOI: 10.1002/cpdd.1110 -
BioMed Research International 2023Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the...
BACKGROUND
Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the goal of this study was to see if it caused bone loss through gastrin secretion.
METHODS
Forty male rats were divided into control, octreotide (Oct), pantoprazole (Pan), and pantoprazole plus octreotide (Pan+Oct) groups. Serum calcium, phosphorous, alkaline phosphatase, parathyroid hormone, and gastrin were measured before and three months after the treatment, and bone densitometry was examined. The rats' femoral bones were examined stereologically at the end of the investigation.
RESULTS
The Pan group had considerably greater levels of serum alkaline phosphatase, parathyroid hormone (PTH), and gastrin, but this was prevented in the presence of Oct, a gastrin secretion inhibitor. All parameters of femoral bone densitometry in the Pan group were significantly lower than the control after treatment which was considerably inhibited in the presence of Oct. Furthermore, when compared to the control and Oct groups, the rats in the Pan group had a lower trabecular volume, femur bone weight, and volume, as well lower number of osteocytes. The amount of osteoclasts, on the other hand, was much higher in the Pan group than in the other groups.
CONCLUSION
Overall findings revealed that pantoprazole caused bone loss, which could be prevented by adding octreotide. Because these detrimental effects were not detected in rats given both Oct and Pan, it was suggested that the effect of Pan on bone was produced by a hypergastrinemic condition.
Topics: Male; Animals; Rats; Pantoprazole; Gastrins; Alkaline Phosphatase; Octreotide; Bone Diseases, Metabolic; Parathyroid Hormone
PubMed: 37711876
DOI: 10.1155/2023/2594664 -
Trials Aug 2023Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use...
Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial.
BACKGROUND
Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes in patients with and without COVID-19 infection.
METHODS
The ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection.
DISCUSSION
Prophylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research.
TRIAL REGISTRATION
REVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023].
Topics: Humans; Proton Pump Inhibitors; Pantoprazole; Respiration, Artificial; Cohort Studies; Critical Illness; Venous Thromboembolism; COVID-19; Gastrointestinal Hemorrhage; Randomized Controlled Trials as Topic
PubMed: 37644556
DOI: 10.1186/s13063-023-07589-2 -
Arquivos de Gastroenterologia 2023•In eradication treatment of H. pylori gemifloxacin containing triple treatment regimen was as effective as bismuth containing quadruple treatment. •Drug adverse...
•In eradication treatment of H. pylori gemifloxacin containing triple treatment regimen was as effective as bismuth containing quadruple treatment. •Drug adverse effects were fewer and milder in the gemifloxacin group. •Since treatment period was shorter and pills to be taken were fewer compared to quadruple treatment, patient compliance was significantly higher in the gemifloxacin group. Background - After eradication of Helicobacter pylori (H. pylori) chronic gastritis will resolve, complications due to H. pylori infection and recurrence of infection will be prevented. Objective - To determine efficacy and safety of gemifloxacin containing treatment regimen in first line treatment of H. pylori with comparison to bismuth containing quadruple therapy. Methods - This retrospective study was conducted in a tertiary care university hospital between January 2018 and January 2021 with 410 participants who were diagnosed to have H. pylori infection with biopsies obtained during upper gastrointestinal system endoscopy. Patients were distributed into two groups according to their first-line treatment regimens. First group patients were treated with amoxicillin, gemifloxacin and pantoprazole and second group patients were treated with amoxicillin, metronidazole, bismuth subcitrate and pantoprazole for seven days. Results - Intention to treat and per protocol ratios for gemifloxacin containing regimen were 90.0% and 91.2%, while quadruple treatment has these ratios as 91.7% and 93.8% respectively. Treatment success rate in both regimens were similar. But adverse effects were lower and patient compliance were better in patients who had gemifloxacin containing treatment (P<0.001). Conclusion - Gemifloxacin containing treatment regimen is as effective as bismuth containing quadruple treatment regimen for H. pylori infection and patient compliance is better in this group. Gemifloxacin containing treatment regimens may be novel and effective alternatives for eradication of H. pylori infection.
Topics: Humans; Gemifloxacin; Helicobacter pylori; Bismuth; Pantoprazole; Retrospective Studies; Drug Therapy, Combination; Helicobacter Infections; Amoxicillin; Metronidazole; Treatment Outcome; Gastritis; Anti-Bacterial Agents; Proton Pump Inhibitors
PubMed: 37792765
DOI: 10.1590/S0004-2803.230302-23-51 -
Journal of Gastroenterology and... Jun 2017Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against... (Review)
Review
Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anticoagulants; Asian People; Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; Dexlansoprazole; Drug Interactions; Drug Therapy, Combination; Asia, Eastern; Gastroesophageal Reflux; Gastrointestinal Hemorrhage; Humans; Isoenzymes; Pantoprazole; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Proton Pump Inhibitors; Rabeprazole; Ticlopidine
PubMed: 28024166
DOI: 10.1111/jgh.13712 -
Frontiers in Oncology 2021The effective and economical therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC) is still requested from patients, who are not available for...
The effective and economical therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC) is still requested from patients, who are not available for Lu-177 or Ra-223 treatment. Drug repurposing as a cost-effective and time-saving alternative to traditional drug development has been increasingly discussed. Proton pump inhibitors (PPIs) such as pantroprazole, which are commonly used as antacids, have also been shown to be effective in cancer chemoprevention induction of apoptosis in multiple cancer cell lines. Vitamin C is an essential micronutrient for human body, has been proposed as a potential anti-cancer agent. In this context, have we investigated the combination of vitamin C and pantoprazole for the management of metastatic castration-resistant prostate cancer (mCRPC). Six chosen human adenocarcinoma cell lines were used to investigate the influence of pantoprazole on the microenvironment of cancer cells (extracellular pH and production of exosomes). Tumor growth and tumor 18F-FDG uptake in PC3 xenografts were analyzed following varied treatment. Our Results have suggested that pantoprazole enhanced the cytotoxic activity of vitamin C by regulating pH values and production of exosomes in cancer cells. Moreover, the synergistic effect of pantoprazole and vitamin C was pH-dependent since pantoprazole was more effective at a slightly acidic pH. In vivo, the combined treatment using pantoprazole and vitamin C produced better therapeutic outcomes than treatment with vitamin C or pantoprazole alone, as demonstrated tumor growth and uptake of 18F-FDG. Therefore, we suggest that pantoprazole combined with vitamin C could be as a possible strategy to manage mCRPC.
PubMed: 34307134
DOI: 10.3389/fonc.2021.660320 -
International Journal of Molecular... Jan 2023Proton-pump inhibitors (PPI), e.g., omeprazole or pantoprazole, are the most widely used drugs for various gastrointestinal diseases. However, more and more side...
Proton-pump inhibitors (PPI), e.g., omeprazole or pantoprazole, are the most widely used drugs for various gastrointestinal diseases. However, more and more side effects, especially an increased risk of infections, have been reported in recent years. The underlying mechanism has still not yet been fully uncovered. Hence, in this study, we analyzed the T cell response after treatment with pantoprazole in vitro. Pantoprazole preincubation reduced the production and secretion of interferon (IFN)-γ and interleukin (IL)-2 after the T cells were activated with phytohemagglutinin (PHA)-L or toxic shock syndrome toxin-1 (TSST-1). Moreover, a lower zinc concentration in the cytoplasm and a higher concentration in the lysosomes were observed in the pantoprazole-treated group compared to the untreated group. We also tested the expression of the zinc transporter Zrt- and Irt-like protein (Zip)8, which is located in the lysosomal membrane and plays a key role in regulating intracellular zinc distribution after T cell activation. Pantoprazole reduced the expression of Zip8. Furthermore, we measured the expression of cAMP-responsive element modulator (CREM) α, which directly suppresses the expression of IL-2, and the expression of the phosphorylated cAMP response element-binding protein (pCREB), which can promote the expression of IFN-γ. The expression of CREMα was dramatically increased, and different isoforms appeared, whereas the expression of pCREB was downregulated after the T cells were treated with pantoprazole. In conclusion, pantoprazole downregulates IFN-γ and IL-2 expression by regulating the expression of Zip8 and pCREB or CREMα, respectively.
Topics: Proton Pump Inhibitors; Pantoprazole; Interleukin-2; 2-Pyridinylmethylsulfinylbenzimidazoles; Zinc; T-Lymphocytes; Acids
PubMed: 36674704
DOI: 10.3390/ijms24021191 -
The Journal of the Association of... Oct 2023: To evaluate the effectiveness of rabeprazole and other proton pump inhibitors (PPIs) in providing symptomatic relief in patients with varying severity of...
: To evaluate the effectiveness of rabeprazole and other proton pump inhibitors (PPIs) in providing symptomatic relief in patients with varying severity of gastroesophageal reflux disease (GERD). : In this multicenter retrospective study, electronic medical records (EMRs) of GERD patients prescribed with PPIs at two Indian clinics/hospitals were reviewed (2016-2020). Rabeprazole's effectiveness was assessed at different follow-up visits and compared with other PPIs. : Overall, 269 patients (moderate and severe GERD: 84.39%) were included in three groups, rabeprazole, pantoprazole, and esomeprazole groups. A significant proportion of patients experienced quick and complete symptomatic relief at visit 1 with rabeprazole compared to the baseline visit, which gradually increased till visit 4 for both daytime [ heartburn (38.78-93.88%; < 0.001)] and nocturnal symptoms [ sleep disturbances (62.92-97.75%; < 0.001)]. Rabeprazole provided quick relief at visit 1 when compared with pantoprazole for daytime heartburn (38.78 vs 5.56%; = 0.01), daytime epigastric pain (66.04 vs 12.12%; = 0.049), and nocturnal water brash (60.71 vs 16.13%; = 0.015), and when compared with esomeprazole for nocturnal nausea (82.61 vs 20.00%; = 0.013). Further, the proportion of patients exhibiting complete treatment response was relatively higher in the rabeprazole group (83.33%) than in the pantoprazole (62.07%) and esomeprazole (65.67%) groups at visit 4. : Rabeprazole was effective in providing quick and sustained relief for both daytime and nocturnal GERD symptoms in patients with moderate and severe GERD. Rabeprazole also demonstrated greater effectiveness when compared with pantoprazole and esomeprazole in reducing the severity of multiple GERD symptoms. : Lawate P, Jilawar N, Vyas K, Effectiveness of Rabeprazole and Other Proton Pump Inhibitors in Managing GERD with Varying Severity: A Retrospective, Real-world EMR-based Study (POWER GERD Study). J Assoc Physicians India 2023;71(10):37-44.
Topics: Humans; Proton Pump Inhibitors; Gastroesophageal Reflux; Rabeprazole; Retrospective Studies; Male; Female; Middle Aged; Severity of Illness Index; Adult; Pantoprazole; Esomeprazole; Treatment Outcome; Electronic Health Records
PubMed: 38716522
DOI: 10.59556/japi.71.0366