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Pharmaceutical Biology Dec 2019Omeprazole and astragaloside IV (AS-IV) are widely used for the treatment of gastric ulcers in China clinics. This study investigates the effects of AS-IV on the...
Omeprazole and astragaloside IV (AS-IV) are widely used for the treatment of gastric ulcers in China clinics. This study investigates the effects of AS-IV on the pharmacokinetics of omeprazole in rats. The pharmacokinetics of orally administered omeprazole (2 mg/kg), with or without AS-IV (100 mg/kg/day for 7 days) pretreatment, were investigated in male Sprague-Dawley rats (two groups of six animals each) using LC-MS/MS. A Caco-2 cell transwell model and rat liver microsome incubation systems were also used to support the pharmacokinetic data and investigate its potential mechanism. The results indicated that co-administration of AS-IV could decrease the systemic exposure of omeprazole significantly ( < 0.05), including AUC (717.20 ± 177.63 vs. 1166.25 ± 186.65 ng h/mL) and (272.35 ± 25.81 vs. 366.34 ± 32.57 ng/mL). The of omeprazole also decreased significantly (1.78 ± 0.15 vs. 2.23 ± 0.27 h, < 0.05). The efflux ratio of omeprazole across the Caco-2 cell transwell model increased significantly from 1.73 to 2.67 ( < 0.05), and the metabolic stability of omeprazole was decreased from 42.6 ± 7.8 to 26.2 ± 5.1 min with the pretreatment of AS-IV ( < 0.05). AS-IV could decrease the systemic exposure of omeprazole in rats when AS-IV and omeprazole were co-administered, and it might exert these effects through decreasing the absorption of omeprazole by inducing , or through accelerating the metabolism of omeprazole in rat liver by inducing the activity of CYP3A4.
Topics: Animals; Caco-2 Cells; Humans; Male; Microsomes, Liver; Omeprazole; Rats; Rats, Sprague-Dawley; Saponins; Triterpenes
PubMed: 31290355
DOI: 10.1080/13880209.2019.1636828 -
The Journal of Toxicological Sciences 2023Long-term use of proton pump inhibitors (PPIs) is known to clinically induce hypomagnesemia, increasing the risk toward QT-interval prolongation and lethal ventricular...
In vivo analysis of acute eletropharmacological effects of proton pump inhibitors using halothane-anesthetized dogs: a translational study of cardiovascular adverse events.
Long-term use of proton pump inhibitors (PPIs) is known to clinically induce hypomagnesemia, increasing the risk toward QT-interval prolongation and lethal ventricular arrhythmias, whereas PPIs can directly modulate cardiac ionic currents in the in vitro experiments. In order to fill the gap between those information, we assessed acute cardiohemodynamic and electrophysiological effects of sub- to supra-therapeutic doses (0.05, 0.5 and 5 mg/kg/10 min) of typical PPIs omeprazole, lansoprazole and rabeprazole, using halothane-anesthetized dogs (n = 6 for each drug). The low and middle doses of omeprazole and lansoprazole increased or tended to increase the heart rate, cardiac output and ventricular contraction, whereas the high dose plateaued and decreased them. Meanwhile, the low and middle doses of omeprazole and lansoprazole decreased the total peripheral vascular resistance, whereas the high dose plateaued and increased it. Rabeprazole decreased the mean blood pressure in a dose-related manner; moreover, its high dose decreased the heart rate and tended to reduce the ventricular contractility. On the other hand, omeprazole prolonged the QRS width. Omeprazole and lansoprazole tended to prolong the QT interval and QTcV, and rabeprazole mildly but significantly prolonged them in a dose-related manner. High dose of each PPI prolonged the ventricular effective refractory period. Omeprazole shortened the terminal repolarization period, whereas lansoprazole and rabeprazole hardly altered it. In effects, PPIs can exert multifarious cardiohemodynamic and electrophysiological actions in vivo, including mild QT-interval prolongation; thus, PPIs should be given with caution to patients with reduced ventricular repolarization reserve.
Topics: Dogs; Animals; Proton Pump Inhibitors; Rabeprazole; Halothane; Omeprazole; Lansoprazole
PubMed: 37394651
DOI: 10.2131/jts.48.375 -
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 -
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 -
Clinical and Experimental Dental... Oct 2022Proton pump inhibitors, such as omeprazole and pantoprazole, are frequently prescribed for the treatment of acid reflux. However, those medications have been shown to... (Review)
Review
OBJECTIVES
Proton pump inhibitors, such as omeprazole and pantoprazole, are frequently prescribed for the treatment of acid reflux. However, those medications have been shown to affect a variety of physiologic processes, including bone homeostasis and the gastrointestinal microbiome. The objective of this study was to assess the relationship between proton pump inhibitors and attachment levels around teeth and dental implants. A scoping review was performed to assess the extent and quality of the relevant literature.
MATERIALS AND METHODS
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) and searched four relevant biomedical literature databases in addition to the grey literature. Keywords in the title and abstract fields, and subject headings for proton pump inhibitors, teeth, and dental implants were included as search terms.
RESULTS
Overall search results identified 791 publications which, after applying the inclusion and exclusion criteria, yielded 27 publications that were further analyzed for relevance and quality of scientific evidence. The majority of eligible publications were retrospective cohort studies. Following critical analysis, 13 publications, including six abstracts, were used to assess the effect of proton pump inhibitors on tissue attachment around teeth and dental implants.
CONCLUSIONS
There are few high-quality studies describing the effect of proton pump inhibitors on tissue attachment around teeth and dental implants. Nevertheless, among the included papers with the fewest confounding factors, there was a positive relationship between proton pump inhibitors and soft tissue attachment levels around teeth, and a predominantly negative but variable effect of proton pump inhibitors on the bone level around dental implants. Additional well-controlled prospective studies are required to fully elucidate those relationships.
Topics: Dental Implants; Humans; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Retrospective Studies
PubMed: 35799099
DOI: 10.1002/cre2.616 -
The Journal of Allergy and Clinical... May 2021Proton pump inhibitors (PPIs) have been recognized as a primary treatment of eosinophilic esophagitis (EoE), an allergic inflammatory disease of the esophageal mucosa....
BACKGROUND
Proton pump inhibitors (PPIs) have been recognized as a primary treatment of eosinophilic esophagitis (EoE), an allergic inflammatory disease of the esophageal mucosa. The mechanisms underlying esophageal epithelial responses to PPIs remain poorly understood.
OBJECTIVE
We hypothesized that PPIs can counteract IL-13-mediated esophageal epithelial responses that are germane for EoE pathogenesis.
METHODS
Transcriptional responses of human esophageal cells to IL-13 and the PPIs omeprazole and esomeprazole were assessed by RT-PCR and RNA sequencing. Cytokine secretion was measured by multiplex analysis and ELISA.
RESULTS
Human esophageal epithelial cells robustly responded to PPI stimulation by inducing a set of 479 core genes common between omeprazole and esomeprazole treatments. The transcriptional response to PPIs was partially mediated through the aryl hydrocarbon receptor signaling pathway, as the aryl hydrocarbon receptor antagonist GNF-351 modified approximately 200 genes, particularly those enriched in metabolic processes and regulation of cell death. PPI treatment reversed approximately 20% of the IL-13 transcriptome. Functional analysis of the PPI-responsive, upregulated genes revealed enrichment in metabolic and oxidation processes, and the unfolded protein response. In contrast, downregulated genes were overrepresented in functional terms related to cell division and cytoskeletal organization, which were also enriched for the genes in the EoE transcriptome reversed by PPIs. Furthermore, PPI treatment decreased the IL-13-induced proliferative response of esophageal epithelial cells.
CONCLUSIONS
These results demonstrate broad effects of PPIs on esophageal epithelium, including their ability to curtail transcriptomic processes involved in cellular proliferation and IL-13-induced responses, and they highlight the importance of AHR signaling in mediating these responses.
Topics: Animals; Cell Line; Eosinophilic Esophagitis; Epithelial Cells; Esophageal Mucosa; Humans; Interleukin-13; Mice; Omeprazole; Proton Pump Inhibitors; Receptors, Aryl Hydrocarbon; Transcription, Genetic
PubMed: 33289661
DOI: 10.1016/j.jaci.2020.09.039 -
BMC Pharmacology & Toxicology May 2017Poor drug quality is a matter of serious concern, especially in countries where drug regulation and law enforcement are constrained by limited resources. This study was...
BACKGROUND
Poor drug quality is a matter of serious concern, especially in countries where drug regulation and law enforcement are constrained by limited resources. This study was carried out to investigate the cause of quality failure of omeprazole in Cambodia in 2010 and Myanmar in 2014.
METHODS
We conducted pharmacopoeial quantity, content uniformity and dissolution tests of 156 samples of omeprazole capsules collected in Cambodia in 2010 and Myanmar in 2014. High failure rates were found, especially in dissolution testing, and detailed investigation of several unacceptable samples was carried out by means of in-vitro dissolution profiling, scanning electron microscopy (SEM) and X-ray computed tomography (X-ray CT) to identify the cause of failure.
RESULTS
Dissolution profiling with and without the acid stage showed that acid caused premature omeprazole release, indicating that the enteric coating of the omeprazole granules was ineffective. SEM examination of two failed samples revealed cracked and broken granules mixed with apparently intact omeprazole granules in the capsule. X-ray CT examination indicated that some granules of failed samples completely lacked enteric coating, and others had incomplete and non-uniform enteric coating or malformation.
CONCLUSIONS
Omeprazole capsules collected in Myanmar and Cambodia showed high failure rates in pharmacopoeial tests, especially dissolution tests. Some samples were found to have ineffective or absent enteric coating of the granules, resulting in premature dissolution and degradation in acidic conditions. This is a potentially serious public health issue that needs to be addressed by regulatory authorities in Cambodia and Myanmar, possibly through a collaborative initiative with manufacturers.
Topics: Cambodia; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Drug Compounding; Drug Industry; Microscopy, Electron, Scanning; Myanmar; Omeprazole; Product Surveillance, Postmarketing; Tomography, X-Ray Computed
PubMed: 28468688
DOI: 10.1186/s40360-017-0138-5 -
The Turkish Journal of Gastroenterology... Dec 2023Proton pump inhibitors are frequently used to treat gastroesophageal reflux disease, but their effect is restricted. The present study aimed to investigate whether the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIMS
Proton pump inhibitors are frequently used to treat gastroesophageal reflux disease, but their effect is restricted. The present study aimed to investigate whether the addition of sublingual melatonin to omeprazole was effective in the treatment of gastro gastroesophageal reflux disease symptoms.
MATERIALS AND METHODS
This was a randomized double-blind clinical trial. A total of 78 patients with gastro gastroesophageal reflux disease were randomly allocated to either omeprazole 20 mg/d plus sublingual melatonin (3 mg/d) or omeprazole 20 mg/d plus placebo for 4 weeks. The selected patients had histories of heartburn and regurgitation and a score ≤32 on the Frequency Scale for the Symptoms of gastroesophageal reflux disease (FSSG). The outcome measures for the assessment of treatment efficacy were heartburn, epigastric pain and the Frequency Scale for the Symptoms of gastroesophageal reflux disease score. Safety and quality of life were evaluated in the patients as the secondary outcomes too.
RESULTS
Seventy-two out of 78 eligible patients completed this trial (35 in the melatonin group and 37 in the placebo group). Heartburn, epigastric pain, and Frequency Scale for the Symptoms of gastroesophageal reflux disease score declined significantly in the melatonin group compared to the placebo group (P = .04, P = .03, and P = .0001, respectively). Moreover, the quality of life score was significantly higher in the melatonin group compared with the placebo group (P = .0001). Adverse events were similarly observed in the 2 groups (P = .55), and there were no serious adverse events.
CONCLUSION
The combination of sublingual melatonin (3 mg/day) with omeprazole (20 mg/day) may be more effective than omeprazole (20 mg/day) alone in the treatment of gastroesophageal reflux disease.
Topics: Humans; Omeprazole; Heartburn; Melatonin; Quality of Life; Gastroesophageal Reflux; Proton Pump Inhibitors; Treatment Outcome; Pain; Double-Blind Method
PubMed: 37768310
DOI: 10.5152/tjg.2023.23021 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2021The aim: Of the study was to study the activity of superoxide dismutase and catalase in the gastric mucosa of rats under long-term administration of omeprazole and...
ACTIVITY OF SUPEROXIDE DISMUTASE AND CATALASE IN THE GASTRIC MUCOSA OF RATS UNDER THE PROLONGED ADMINISTRATION OF OMEPRAZOL AND COMBINATION OF OMEPRAZOLE AND MULTIPROBIOTICS.
OBJECTIVE
The aim: Of the study was to study the activity of superoxide dismutase and catalase in the gastric mucosa of rats under long-term administration of omeprazole and combined administration of omeprazole with Symbiter and Apibact multiprobiotics.
PATIENTS AND METHODS
Materials and methods: The study was carried out on 40 white non-linear male rats with an initial weight of 160-180 g. All animals were divided into 4 groups. Group I was the control. Group II was administered omeprazole once a day within the period of 28 days. Group III was administered a combination of omeprazole and Symbiter® multiprobiotic. Group IV was administered a combination of omeprazole and Apibact® multiprobiotic. The activity of superoxide dismutase in cells was determined by Chevars et al. . The catalase activity in cells was determined by Korolyuk et al. . Statistical processing of the results was performed using the "Statistica 7.0" software.
RESULTS
Results: The activity of SOD and catalase in the gastric mucosa of rats after 28 days of omeprazole administration increased compared to the control. Probiotics reduced the activity of SOD compared to the group of rats where omeprazole only was administered. The catalase activity in the gastric mucosa of rats which were jointly administered omeprazole and multiprobiotics for 28 days did not statistically significantly differ from the similar index in the control group.
CONCLUSION
Conclusions: Prolonged gastric juice hypochlorhydria led to depletion of antioxidant protection enzymes. Multiprobiotics reduced the manifestation of the inflammatory process in the gastric mucosa.
Topics: Achlorhydria; Animals; Catalase; Gastric Mucosa; Male; Omeprazole; Superoxide Dismutase
PubMed: 33813494
DOI: No ID Found -
Molecules (Basel, Switzerland) Aug 2022Currently, studies are being conducted on the possible role of the cytoprotective effect of biologically active substances in conditions of cerebral hypoxia or...
Currently, studies are being conducted on the possible role of the cytoprotective effect of biologically active substances in conditions of cerebral hypoxia or cardiomyopathies. At the same time, oxidative stress is considered one of the important mechanisms of cellular cytotoxicity and a target for the action of cytoprotectors. The aim of this study is to search for derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1)-ones. The probability of cytoprotective action was assessed by measuring cell viability using two tests (with neutral red dye and MTT test). It was found that some derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1)-ones under the conditions of our experiment had a pronounced cytoprotective activity, providing better cell survival in vitro, including the MTT test and conditions of blood hyperviscosity. To correlate the obtained results in vitro, molecular docking of the synthesized derivatives was also carried out. The standard drug omeprazole (co-crystallized with the enzyme) was used as a standard. It was shown that all synthesized derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1)-ones had higher affinity for the selected protein than the standard gastro-cytoprotector omeprazole. The studied derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1)-ones also fully satisfy Lipinski's rule of five (RO5), which increases their chances for possible use as orally active drugs with good absorption ability and moderate lipophilicity. Thus, the results obtained make it possible to evaluate derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1)-ones as having a relatively high cytoprotective potential.
Topics: Cell Survival; Molecular Docking Simulation; Omeprazole; Structure-Activity Relationship
PubMed: 36080132
DOI: 10.3390/molecules27175362