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Alimentary Pharmacology & Therapeutics Sep 2015Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases. Vonoprazan is a member of a new class of acid suppressants;... (Comparative Study)
Comparative Study Randomized Controlled Trial
Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or rabeprazole 10 mg in healthy adult male subjects--a randomised open-label cross-over study.
BACKGROUND
Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases. Vonoprazan is a member of a new class of acid suppressants; potassium-competitive acid blockers. Vonoprazan may thus be an alternative to PPIs.
AIM
To evaluate efficacy, rapidity and duration of acid-inhibitory effects of vonoprazan vs. two control PPIs, esomeprazole and rabeprazole, in 20 healthy Japanese adult male volunteers with CYP2C19 extensive metaboliser genotype.
METHODS
In this randomised, open-label, two-period cross-over study, vonoprazan 20 mg and esomeprazole 20 mg (Study V vs. E) or rabeprazole 10 mg (Study V vs. R) were orally administered daily for 7 days. Primary pharmacodynamic endpoint was gastric pH over 24 h measured as percentage of time pH ≥3, ≥4 and ≥5 (pH holding time ratios; HTRs) and mean gastric pH.
RESULTS
Acid-inhibitory effect (pH4 HTR) of vonoprazan was significantly greater than that of esomeprazole or rabeprazole on both Days 1 and 7; Day 7 difference in pH4 HTR for vonoprazan vs. esomeprazole was 24.6% [95% confidence interval (CI): 16.2-33.1] and for vonoprazan vs. rabeprazole 28.8% [95% CI: 17.2-40.4]. The Day 1 to Day 7 ratio of 24-h pH4 HTRs was >0.8 for vonoprazan, compared with 0.370 for esomeprazole and 0.393 for rabeprazole. Vonoprazan was generally well tolerated. One vonoprazan subject withdrew due to a rash which resolved after discontinuation.
CONCLUSIONS
This study demonstrated a more rapid and sustained acid-inhibitory effect of vonoprazan 20 mg vs. esomeprazole 20 mg or rabeprazole 10 mg. Therefore, vonoprazan may be a potentially new treatment for acid-related diseases.
Topics: Adult; Cross-Over Studies; Esomeprazole; Gastric Acid; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Proton Pump Inhibitors; Pyrroles; Rabeprazole; Research Design; Sulfonamides
PubMed: 26193978
DOI: 10.1111/apt.13325 -
Digestive Diseases and Sciences Mar 2019Proton pump inhibitors and vonoprazan (a potassium-competitive acid blocker) are recommended as first-line treatments for gastroesophageal reflux disease (GERD).... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND AND AIM
Proton pump inhibitors and vonoprazan (a potassium-competitive acid blocker) are recommended as first-line treatments for gastroesophageal reflux disease (GERD). However, few reports have investigated the onset of action of these agents for GERD symptom relief. The present study compared the symptom relief of esomeprazole with that of vonoprazan via monitoring self-reported GERD symptoms after treatment initiation.
METHODS
This was a prospective, multicenter, randomized, open-label, parallel group, comparative clinical study between esomeprazole (20 mg/day) and vonoprazan (20 mg/day) administered for 4 weeks to patients with GERD symptoms. Patients who had scores ≥ 8 on the Gastroesophageal Reflux Disease Questionnaire (GerdQ) were defined as having GERD and enrolled in this study. Sixty patients were randomly assigned to either the esomeprazole group (n = 30) or the vonoprazan group (n = 30). Treatment response rates in each drug group were evaluated according to the GerdQ. The Frequency Scale for the Symptoms of GERD (FSSG) scores from the 1st day after treatment initiation and the Global Overall Symptom (GOS) scale scores during treatment were also evaluated.
RESULTS
At 4 weeks, the treatment response rates for symptom relief according to the GerdQ were 88.0% in the esomeprazole group and 81.8% in the vonoprazan group. The GOS scales, which reflect the impact of GERD symptoms, were similar for both groups. The FSSG scores decreased from the 1st to the 14th day in both groups.
CONCLUSIONS
There were no substantial differences in the symptom relief between the two groups at any time point in this short-term study.
Topics: Adult; Aged; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Japan; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Pyrroles; Remission Induction; Self Report; Sulfonamides; Time Factors; Treatment Outcome
PubMed: 30415407
DOI: 10.1007/s10620-018-5365-0 -
Medicina 2018
Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Drug Therapy, Combination; Humans; Nobel Prize; Omeprazole; Peptic Ulcer
PubMed: 29360084
DOI: No ID Found -
The Turkish Journal of Gastroenterology... Sep 2016Studies on the therapeutic efficacy of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD) have been recently published. In most of... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on intragastrıc pH in extensive metabolizer patients with gastroesophageal reflux disease.
BACKGROUND/AIMS
Studies on the therapeutic efficacy of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD) have been recently published. In most of these studies, comparison of only two PPIs have been made. There are few studies on the comparison of four or more PPIs. We aimed to compare the acid inhibitory effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on days 1 and 5 of treatment in patients with GERD, who were extensive metabolizers in regard to the CYP2C19 genotype.
MATERIALS AND METHODS
Helicobacter pylori-negative with typical symptoms of GERD patients were randomly divided into four treatment groups. Efficacy analysis on days 1 and 5 were performed on the four groups which comprised 10 (esomeprazole), 11 (rabeprazole), 10 (lansoprazole), and 10 (pantoprazole) patients.
RESULTS
On day 1 of PPI treatment, the mean percentage of time with intragastric Ph>4 were 54%, 58%, 60%, and 35% for the groups, respectively, and on day 5, these values were 67%, 60%, 68%, and 59%, respectively. Esomeprazole, rabeprazole, and lansoprazole were found to be superior to pantoprazole on the first day of treatment.
CONCLUSION
Pantoprazole is a less potent proton pump inhibitor than the other PPIs tested on the first day of treatment. When the time needed to raise the intragatric pH to over 4 was evaluated, esomeprazole was found to have the most rapid action, followed by lansoprazole and rabeprazole.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Cross-Over Studies; Cytochrome P-450 CYP2C19; Double-Blind Method; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Genotype; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Treatment Outcome
PubMed: 27782887
DOI: 10.5152/tjg.2016.15514 -
Sao Paulo Medical Journal = Revista... 2018Risks regarding hospital admission due to adverse drug reactions and drug interactions from use of omeprazole have been reported. The question guiding the present review... (Review)
Review
BACKGROUND
Risks regarding hospital admission due to adverse drug reactions and drug interactions from use of omeprazole have been reported. The question guiding the present review was "Which adverse events occur in patients using omeprazole in a Food and Drug Administration-approved and/or off-label manner?" It was also proposed to evaluate the safety of use of omeprazole.
DESIGN AND SETTING
Qualitative narrative review with critical evaluation, in a public university.
METHODS
The PubMed, SCOPUS, LILACS, SciELO, EMBASE and EBSCO databases were searched on July 31, 2018. Studies evaluating adverse events were screened.
RESULTS
72 articles were included, among which 58 reported on adverse drug events (47, adverse drug reactions; 5, drug interactions; and 6, situations of ineffectiveness). 28 adverse drug reactions not described in compendia and drug leaflets were described in these studies: myocardial infarction (6); stroke (2); spontaneous abortion (1); proliferative changes (1); chills (1); heart failure (1); thrombosis (2); and dementia (1), among others. Severe adverse reactions, for instance cardiac problems, Steven-Johnson syndrome and proliferative changes, were identified. The antiplatelet effects of drugs such as clopidogrel, in patients who underwent heart-related surgery, increased the risk of developing cardiac problems, such as cardiovascular death, myocardial infarction and stroke. In newly transplanted patients, decreased absorption of mycophenolate mofetil occurred, thus leading to rejection of transplanted organs.
CONCLUSION
Use of omeprazole should be monitored primarily in patients with heart disorders using antiplatelet agents concomitantly, and in newly transplanted patients using mycophenolic acid, in order to avoid serious adverse reactions.
Topics: Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Drug Interactions; Humans; Omeprazole; Peptic Ulcer; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome
PubMed: 30892487
DOI: 10.1590/1516-3180.2018.0019220318 -
Redox Biology May 2020Omeprazole, a proton pump inhibitor used to treat peptic ulcer and gastroesophageal reflux disease, has been associated to chronic kidney disease and acute interstitial...
Omeprazole, a proton pump inhibitor used to treat peptic ulcer and gastroesophageal reflux disease, has been associated to chronic kidney disease and acute interstitial nephritis. However, whether omeprazole is toxic to renal cells is unknown. Omeprazole has a lethal effect over some cancer cells, and cell death is a key process in kidney disease. Thus, we evaluated the potential lethal effect of omeprazole over tubular cells. Omeprazole induced dose-dependent cell death in human and murine proximal tubular cell lines and in human primary proximal tubular cell cultures. Increased cell death was observed at the high concentrations used in cancer cell studies and also at lower concentrations similar to those in peptic ulcer patient serum. Cell death induced by omeprazole had features of necrosis such as annexin V/7-AAD staining, LDH release, vacuolization and irregular chromatin condensation. Weak activation of caspase-3 was observed but inhibitors of caspases (zVAD), necroptosis (Necrostatin-1) or ferroptosis (Ferrostatin-1) did not prevent omeprazole-induced death. However, omeprazole promoted a strong oxidative stress response affecting mitochondria and lysosomes and the antioxidant N-acetyl-cysteine reduced oxidative stress and cell death. By contrast, iron overload increased cell death. An adaptive increase in the antiapoptotic protein BclxL failed to protect cells. In mice, parenteral omeprazole increased tubular cell death and the expression of NGAL and HO-1, markers of renal injury and oxidative stress, respectively. In conclusion, omeprazole nephrotoxicity may be related to induction of oxidative stress and renal tubular cell death.
Topics: Animals; Apoptosis; Cell Death; Humans; Kidney; Mice; Necrosis; Omeprazole; Oxidative Stress
PubMed: 32092686
DOI: 10.1016/j.redox.2020.101464 -
Oxidative Medicine and Cellular... 2020Omeprazole (OME) is commonly used to treat gastrointestinal disorders. However, long-term use of OME can increase the risk of gastric cancer. We aimed to characterize... (Review)
Review
Omeprazole (OME) is commonly used to treat gastrointestinal disorders. However, long-term use of OME can increase the risk of gastric cancer. We aimed to characterize the pharmacological effects of OME and to correlate its adverse effects and toxicogenetic risks to the genomic instability mechanisms and cancer-based on database reports. Thus, a search (till Aug 2019) was made in the PubMed, Scopus, and ScienceDirect with relevant keywords. Based on the study objective, we included 80 clinical reports, forty-six , and 76 studies. While controversial, the findings suggest that long-term use of OME (5 to 40 mg/kg) can induce genomic instability. On the other hand, OME-mediated protective effects are well reported and related to proton pump blockade and anti-inflammatory activity through an increase in gastric flow, anti-inflammatory markers (COX-2 and interleukins) and antiapoptotic markers (caspases and BCL-2), glycoprotein expression, and neutrophil infiltration reduction. The reported adverse and toxic effects, especially in clinical studies, were atrophic gastritis, cobalamin deficiencies, homeostasis disorders, polyp development, hepatotoxicity, cytotoxicity, and genotoxicity. This study highlights that OME may induce genomic instability and increase the risk of certain types of cancer. Therefore, adequate precautions should be taken, especially in its long-term therapeutic strategies and self-medication practices.
Topics: Animals; Genomic Instability; Humans; Neoplasms; Omeprazole; Proton Pump Inhibitors; Rats
PubMed: 32308801
DOI: 10.1155/2020/3457890 -
Acta Bio-medica : Atenei Parmensis Jun 2023Hydrochloric acid is crucial in gastric physiology. In 1978 cimetidine, the first H2 antagonist of histamine receptors on the gastric parietal cell was introduced into...
Hydrochloric acid is crucial in gastric physiology. In 1978 cimetidine, the first H2 antagonist of histamine receptors on the gastric parietal cell was introduced into therapy, inducing acid. Lasting the years, several studies focused on the potential relationship between inducing hypo-achlorhydria and risk of developing gastric cancer. In 1988 omeprazole, the first proton pump inhibitor, entered therapy. In 1996, Kuipers underlined the danger of progression of chronic atrophic gastritis in subjects taking PPIs. In 2018, one paper from Korea and an another on from Sweden suggested a possible relationship between long-term PPI therapy and the development of gastric cancer. Over the years, several articles, meta-analyzes and population based focused on relationship between long-term of PPI use and the onset of gastric cancer, with conflicting results. As reported, the presence of bias in the collection of cases, in particular concerning the evaluation of the H.p. status and presence of atrophic gastritis and intestinal metaplasia in subjects treated with PPI, can lead to noticeable errors in the results and conclusions, as demonstrated in the literature by exhaustive methodological studies of pharmacoepidemiology. A possible bias in the collection of case histories is due to the fact that PPIs are often administered to dyspeptic patients, among which there are patients already carriers of gastric neoplasia: the so-called inverse causality. Literature data, amended by methodological bias (sampling errors, lack of comparative assessment of Hp status and atrophic gastritis) NOT support a causal relationship between long-term PPIs therapy and the onset of gastric cancer.
Topics: Humans; Gastritis, Atrophic; Stomach Neoplasms; Proton Pump Inhibitors; Omeprazole; Causality
PubMed: 37326271
DOI: 10.23750/abm.v94i3.14105 -
European Journal of Clinical... Jan 2023The aim of this study was to explore the time-course of hospitalization due to hyponatremia associated with omeprazole and esomeprazole.
PURPOSE
The aim of this study was to explore the time-course of hospitalization due to hyponatremia associated with omeprazole and esomeprazole.
METHODS
In this register-based case-control study, we compared patients hospitalized with a main diagnosis of hyponatremia (n = 11,213) to matched controls (n = 44,801). We used multiple regression to investigate time-related associations between omeprazole and esomeprazole and hospitalization because of hyponatremia.
RESULTS
The overall adjusted OR (aOR) between proton pump inhibitor (PPI) exposure, regardless of treatment duration and hospitalization with a main diagnosis of hyponatremia, was 1.23 (95% confidence interval CI 1.15-1.32). Exposure to PPIs was associated with a prompt increase in risk of hospitalization for hyponatremia from the first week (aOR 6.87; 95% CI 4.83-9.86). The risk then gradually declined, reaching an aOR of 1.64 (0.96-2.75) the fifth week. The aOR of ongoing PPI treatment was 1.10 (1.03-1.18).
CONCLUSION
The present study shows a marked association between omeprazole and esomeprazole and hyponatremia related to recently initiated treatment. Consequently, newly initiated PPIs should be considered a potential culprit in any patient suffering from hyponatremia. However, if the patient has had this treatment for a longer time, the PPI should be considered a less likely cause.
Topics: Humans; Esomeprazole; Omeprazole; Case-Control Studies; Hyponatremia; Proton Pump Inhibitors; Hospitalization
PubMed: 36380227
DOI: 10.1007/s00228-022-03423-x -
BioMed Research International 2024PPIs, or proton pump inhibitors, are the most widely prescribed drugs. There is a debate regarding the relationship between long-term PPI use and the risk of type 2...
INTRODUCTION
PPIs, or proton pump inhibitors, are the most widely prescribed drugs. There is a debate regarding the relationship between long-term PPI use and the risk of type 2 diabetes mellitus (T2DM). A potential connection between T2DM and PPIs could be an elevated gastrin concentration. This study is aimed at investigating the long-term effects of PPI omeprazole (OZ) on glucose homeostasis and pancreatic gene expression profile in mice.
METHODS
Healthy adult male BALB/c mice were randomly divided into three equal groups ( = 10 in each one): (1) experimental mice that received OZ 20 mg/kg; (2) control mice that received 30 l saline per os; (3) intact mice without any interventions. Mice were treated for 30 weeks. Glucose homeostasis was investigated by fasting blood glucose level, oral glucose tolerance test (GTT), insulin tolerance test (ITT), and basal insulin resistance (HOMA-IR). Serum gastrin and insulin concentration were determined by ELISA. Expressions of , , , , , , , and were measured by RT-PCR.
RESULT
The ROC analysis revealed an increase in fasting blood glucose levels in OZ-treated mice in comparison with control and intact groups during the 30-week experiment. A slight but statistically significant increase in glucose tolerance and insulin sensitivity was observed in OZ-treated mice within 30 weeks of the experiment. The mice treated with OZ exhibited significant increases in serum insulin and gastrin levels, accompanied by a rise in the HOMA-IR level. These animals had a statistically significant increase in , , and mRNA expression. There were no differences in -cell numbers between groups.
CONCLUSION
Long-term OZ treatment induced hypergastrin- and hyperinsulinemia and increased expression of , , and in mouse pancreatic tissues accompanied by specific changes in glucose metabolism. The mechanism of omeprazole-induced mRNA expression and its association with pancreatic cancer risk should be investigated.
Topics: Animals; Omeprazole; Gastrins; Male; Mice; Homeostasis; Mice, Inbred BALB C; Blood Glucose; Insulin Resistance; Insulin; Gene Expression Regulation; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Proton Pump Inhibitors; Glucose
PubMed: 38884019
DOI: 10.1155/2024/7747599