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Physiological Reports Apr 2021The present study investigated the effects of Shilajit extract on aspirin-induced gastric lesions in rats. We evaluated macroscopic and histopathological lesions in the...
The present study investigated the effects of Shilajit extract on aspirin-induced gastric lesions in rats. We evaluated macroscopic and histopathological lesions in the stomach, measured the activity of oxidative stress enzymes in gastric tissue homogenates, and assessed serum electrolytes and parameters of kidney and liver function. Forty-five male rats were allocated to five groups: Normal control, positive control, omeprazole treatment, Shilajit treatment, and Shilajit control. The treatment period lasted for four consecutive days. The size and number of gastric lesions were significantly reduced in the Shilajit and omeprazole groups compared to the positive control group, indicating a reduction in mucosal damage and the severity of edema and leukocyte infiltration in tissue sections. A significant increase was observed in the levels of all oxidative stress parameters, except malondialdehyde, in rats treated with Shilajit and omeprazole compared to those in the positive control group. The effect of the aqueous extract of Shilajit was comparable to that of omeprazole. These results indicated the protective effects of Shilajit against aspirin-induced gastric lesions.
Topics: Animals; Antioxidants; Aspirin; Gastric Mucosa; Male; Minerals; Omeprazole; Oxidative Stress; Peptic Ulcer; Rats; Rats, Wistar; Resins, Plant
PubMed: 33818003
DOI: 10.14814/phy2.14822 -
Medicina (Kaunas, Lithuania) Mar 2024The enteric form of omeprazole is one of the most commonly prescribed medications. Similarly to Europe, Kazakhstan relies on the localization of pharmaceutical drug...
The enteric form of omeprazole is one of the most commonly prescribed medications. Similarly to Europe, Kazakhstan relies on the localization of pharmaceutical drug production as one of its primary strategies to ensure that its population has access to affordable and good-quality medicines. This study comprehensively describes the technologically available development of bioequivalent delayed-release omeprazole. Various regimes and technological parameters were tested on laboratory- and production-scale equipment to establish a technical process where a functional and gastro-protective layer is essential. According to the ICH guidance on stability testing and Kazakhstan local rules, stability studies were conducted under conditions appropriate for climate zone II. The comparison of the rate and extent of absorption with subsequent assessment of the bioequivalence of the generic and reference drugs after a single dose of each drug at a dose of 40 mg was performed. The quantitative and qualitative composition and technology of producing a new generic enteric form of omeprazole in capsules were developed and implemented at the manufacturing site of solid forms. Dissolution profiles in media with pH 1.2 and 6.8 were proven. During the accelerated six-month and long-term twelve-month studies, the developed formulation in both packaging materials at each control point passed the average weight and mass uniformity test, dissolution test, acid-resistance stage test, buffer stage test, impurity assay, and microbiological purity test and met all the specification criteria. A bioequivalence study in 24 healthy volunteers compared against the innovative drug showed the bioequivalency of the new generic system. The obtained values from the test and reference products were 1321 ± 249.0 ng/mL and 1274 ± 233 ng/mL for C, 4521 ± 841 ng·h /mL and 4371 ± 695 ng·h /mL for AUC, and 4636 ± 814 ng·h /mL and 4502 ± 640 ng·h /mL for AUC. Using affordable technologies, a bioequivalent generic delayed-release formulation of 20 and 40 mg omeprazole has been developed.
Topics: Humans; Omeprazole; Therapeutic Equivalency; Capsules; Cross-Over Studies; Europe
PubMed: 38541153
DOI: 10.3390/medicina60030427 -
BMC Gastroenterology May 2024Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such...
BACKGROUND
Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs.
METHODS
Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers.
RESULTS
Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy.
CONCLUSIONS
Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.
Topics: Animals; Aspirin; Omeprazole; Rats, Sprague-Dawley; Proton Pump Inhibitors; Gastric Mucosa; Gastrins; Male; Rats; Drug Administration Schedule; Humans; Peptic Ulcer; Intestinal Mucosa; Stomach Ulcer
PubMed: 38811868
DOI: 10.1186/s12876-024-03265-0 -
Journal of Veterinary Internal Medicine Sep 2020Proton pump inhibitors (eg, omeprazole) commonly are administered concurrently with nonsteroidal anti-inflammatory drugs (NSAIDs; eg, carprofen) as prophylaxis to...
BACKGROUND
Proton pump inhibitors (eg, omeprazole) commonly are administered concurrently with nonsteroidal anti-inflammatory drugs (NSAIDs; eg, carprofen) as prophylaxis to decrease the risk of gastrointestinal (GI) injury. However, evidence to support this practice is weak, and it might exacerbate dysbiosis and inflammation.
HYPOTHESIS/OBJECTIVES
To evaluate the effect of carprofen alone or combined with omeprazole in dogs. We hypothesized that coadministration of omeprazole and carprofen would significantly increase GI permeability and dysbiosis index (DI) compared to no treatment or carprofen alone.
ANIMALS
Six healthy adult colony beagle dogs.
METHODS
Gastrointestinal permeability and inflammation were assessed by serum lipopolysaccharide (LPS) concentration, plasma iohexol concentration, fecal DI, and fecal calprotectin concentration in a prospective, 3-period design. In the first 7-day period, dogs received no intervention (baseline). During the 2nd period, dogs received 4 mg/kg of carprofen q24h PO for 7 days. In the 3rd period, dogs received 4 mg/kg of carprofen q24h and 1 mg/kg of omeprazole q12h PO for 7 days. Gastrointestinal permeability testing was performed at the end of each period. Data were analyzed using repeated measures mixed model analysis of variance with Tukey-Kramer post hoc tests (P < .05).
RESULTS
Serum LPS and plasma iohexol concentrations did not differ between treatments. Fecal calprotectin concentrations differed between treatments (P = .03). The DI varied over time based on the treatment received (P = .03). Coadministration of omeprazole and carprofen significantly increased fecal calprotectin concentration and DI compared to baseline and carprofen alone.
CONCLUSIONS AND CLINICAL IMPORTANCE
Omeprazole prophylaxis induces fecal dysbiosis and increases intestinal inflammatory markers when coadministered with carprofen to otherwise healthy dogs with no other risk factors for GI bleeding.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Dog Diseases; Dogs; Female; Inflammation; Male; Omeprazole; Permeability; Prospective Studies
PubMed: 32893926
DOI: 10.1111/jvim.15897 -
Hellenic Journal of Cardiology : HJC =... 2020
Topics: Hemorrhage; Humans; Myocardial Infarction; Omeprazole; Percutaneous Coronary Intervention; Ticagrelor
PubMed: 33181277
DOI: 10.1016/j.hjc.2020.10.002 -
Gaceta Medica de Mexico 2022A national survey in the general population showed that gastroesophageal reflux disease (GERD) is highly prevalent in Mexico. (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
A national survey in the general population showed that gastroesophageal reflux disease (GERD) is highly prevalent in Mexico.
OBJECTIVE
To compare the efficacy and safety of two isomers, dexrabeprazole (10 mg) vs. esomeprazole (20 mg), in the treatment of GERD for four weeks.
METHODS
Randomized, multicenter, prospective, double-blind phase III clinical trial in two groups that included 230 patients.
RESULTS
A statistically significant decrease in the severity of GERD symptoms (heartburn, regurgitation, epigastric pain and dysphagia), evaluated using a visual analogue scale, was observed with both treatments. Mean score for dexrabeprazole on Carlsson-Dent questionnaire at 28 days was 2.12, and for esomeprazole, 3.02. Both treatments were effective, with no statistically significant difference being recorded (p < 0.05). On SF-36 health questionnaire, both were observed to improve the quality-of-life score, with no significant difference being identified. Both drugs were well tolerated, and the adverse event incidence profile was low.
CONCLUSIONS
In the treatment of non-erosive GERD, the use of dexrabeprazole at 10 mg/day is as effective as esomeprazole 20 mg/day, with the advantage that the dose is lower with an appropriate safety profile.
Topics: Humans; Esomeprazole; Rabeprazole; Prospective Studies; Treatment Outcome; Gastroesophageal Reflux
PubMed: 36657136
DOI: 10.24875/GMM.M22000722 -
Clinical and Translational Science May 2022This study evaluated the effect of repeated doses of elagolix on the pharmacokinetics (PK) of omeprazole and its metabolites in healthy premenopausal female subjects....
This study evaluated the effect of repeated doses of elagolix on the pharmacokinetics (PK) of omeprazole and its metabolites in healthy premenopausal female subjects. Adult premenopausal female subjects (N = 20) received a single oral dose of omeprazole (40 mg) on day 1 and day 11 and oral doses of elagolix (300 mg) twice-daily on days 3-11. Serial blood samples for assay of omeprazole and its metabolites were collected for 24 h after dosing on days 1 and 11. PK parameters were calculated for omeprazole, 5-hydroxyomeprazole and omeprazole sulfone; and were compared between day 1 and day 11. Pharmacogenetic testing was performed for CYP2C19 variant alleles and the results were used to compare the magnitude of elagolix-omeprazole drug-drug interaction (DDI) between the different genotype subgroups. Administration of elagolix 300 mg twice-daily for 9 days increased omeprazole exposure by 1.8-fold and decreased the metabolite-to-parent ratio for 5-hydroxyomeprazole by ~60%. Conversely, there was an increase in the metabolite-to-parent ratio for omeprazole sulfone by 25%. Elagolix increased omeprazole exposures by 2- to 2.5-fold in CYP2C19 extensive (EM) and intermediate (IM) metabolizer subjects, but decreased omeprazole exposures by 40% in poor metabolizer subjects. Exposures of 5-hydroxyomeprazole decreased by 20%-30% in all genotype subgroups, and omeprazole sulfone exposures increased by ~3-fold in EM and IM subjects. Elagolix is a weak inhibitor of CYP2C19 and exposure of CYP2C19 substrates may be increased upon coadministration with elagolix. Omeprazole may exhibit drug interactions due to multiple mechanisms other than CYP2C19-mediated metabolism; complicating the interpretation of results from omeprazole DDI studies.
Topics: Adult; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C19; Drug Interactions; Female; Genotype; Humans; Hydrocarbons, Fluorinated; Omeprazole; Pyrimidines
PubMed: 35137535
DOI: 10.1111/cts.13247 -
PloS One 2020Omeprazole is the most commonly used proton pump inhibitor (PPI), a class of medications whose therapeutic mechanism of action involves formation of a disulfide linkage...
Omeprazole is the most commonly used proton pump inhibitor (PPI), a class of medications whose therapeutic mechanism of action involves formation of a disulfide linkage to cysteine residues in the H+/K+ ATPase pump on gastric secretory cells. Covalent linkage between the sole sulfur group of omeprazole and selected cysteine residues of the pump protein results in inhibition of acid secretion in the stomach, an effect that ameliorates gastroesophageal reflux and peptic ulcer disease. PPIs, though useful for specific conditions when used transiently, are associated with diverse untoward effects when used long term. The mechanisms underlying these potential off-target effects remain unclear. PPIs may, in fact, interact with non-canonical target proteins (non-pump molecules) resulting in unexpected pathophysiological effects, but few studies describe off-target PPI binding. Here, we describe successful cloning of monoclonal antibodies against protein-bound omeprazole. We developed and used monoclonal antibodies to characterize the protein target range of omeprazole, stability of omeprazole-bound proteins, and the involvement of cysteines in binding of omeprazole to targets. We demonstrate that a wide range of diverse proteins are targeted by omeprazole. Protein complexes, detected by Western blotting, are resistant to heat, detergents, and reducing agents. Reaction of omeprazole occurs with cysteine-free proteins, is not fully inhibited by cysteine alkylation, occurs at neutral pH, and induces protein multimerization. At least two other clinically used PPIs, rabeprazole and tenatoprazole, are capable of binding to proteins in a similar fashion. We conclude that omeprazole binds to multiple proteins and is capable of forming highly stable complexes that are not dependent on disulfide linkages between the drug and protein targets. Further studies made possible by these antibodies may shed light on whether PPI-protein complexes underlie off-target untoward effects of chronic PPI use.
Topics: Animals; Antibodies, Monoclonal, Murine-Derived; Binding Sites; Cysteine; HEK293 Cells; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Multiprotein Complexes; Omeprazole; Protein Binding; Proton Pump Inhibitors
PubMed: 32946534
DOI: 10.1371/journal.pone.0239464 -
Clinical and Translational Science Oct 2023Our aim was to investigate in a real-life prospective patient cohort how CYP2C19 loss-of-function (LOF) variants and CYP2C19 inhibitor omeprazole or esomeprazole...
Our aim was to investigate in a real-life prospective patient cohort how CYP2C19 loss-of-function (LOF) variants and CYP2C19 inhibitor omeprazole or esomeprazole influence the incidence of cardiovascular events in patients using clopidogrel. Data based simultaneously on these factors are conflicting and sparse. A cohort of prospective patients (n = 1972) with acute coronary syndrome (n = 1302) or symptomatic chronic coronary disease (n = 656) was followed for 365 days after hospitalization with information on purchased prescription drugs, hospital discharge, death, and genotype for CYP2C19*2, CYP2C19*3, and CYP2C19*8 LOF variants. The primary study outcome measurement was cardiovascular death or recurring myocardial infarction or stroke. Altogether, 608 patients (30.8%) carried CYP2C19 LOF alleles. During the 365-day follow-up 252 patients (12.8%) had an ischemic vascular event. Cardiovascular events were significantly more frequent in carriers of CYP2C19 LOF alleles (14.8%, 95% confidence interval [CI], 11.7-17.8) than in non-carriers (10.8%, 95% CI, 9.0-12.6, p = 0.0159). Omeprazole or esomeprazole use was similar among LOF allele carriers (n = 131, 21.5%) and non-carriers (n = 250, 18.3%, p = 0.185). Cardiovascular events were significantly more common in a composite group consisting of all CYP2C19 LOF carriers regardless of proton pump inhibitor use status and non-carriers using omeprazole or esomeprazole than in non-carriers not using omeprazole or esomeprazole (14.8%, 95% CI, 12.2-17.3 vs. 9.9%, 95% CI, 8.0-11.9, p = 0.00173). We observed significantly more cardiovascular events in carriers of CYP2C19 LOF variants and in non-carriers using omeprazole or esomeprazole. For optimal patient care, both genetics and concomitant medication should be considered.
Topics: Humans; Clopidogrel; Platelet Aggregation Inhibitors; Alleles; Esomeprazole; Omeprazole; Cytochrome P-450 CYP2C19; Prospective Studies; Stroke; Genotype; Treatment Outcome
PubMed: 37551775
DOI: 10.1111/cts.13608 -
Basic & Clinical Pharmacology &... Aug 2019
Topics: Cardiovascular Diseases; Cathepsin B; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Endothelium, Vascular; Humans; Lansoprazole; Omeprazole; Oxidative Stress; Proton Pump Inhibitors; Xanthine Dehydrogenase
PubMed: 30980783
DOI: 10.1111/bcpt.13237