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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 Translational Medicine May 2024A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their...
BACKGROUND
A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their causal evidence, however, remains undetermined. The present research endeavors to investigate the underlying causal link between omeprazole and OA through the application of mendelian randomization (MR) analysis.
METHODS
The study incorporated the ukb-a-106 and ukb-b-14,486 datasets. The investigation of causal effects employed methodologies such as MR-Egger, Weighted median, Inverse variance weighted (IVW) with multiplicative random effects, and IVW (fixed effects). The IVW approach was predominantly considered for result interpretation. Sensitivity analysis was conducted, encompassing assessments for heterogeneity, horizontal pleiotropy, and the Leave-one-out techniques.
RESULTS
The outcomes of the MR analysis indicated a causal relationship between omeprazole and OA, with omeprazole identified as a contributing risk factor for OA development (IVW model: OR = 1.2473, P < 0.01 in ukb-a-106; OR = 1.1288, P < 0.05 in ukb-b-14,486). The sensitivity analysis underscored the robustness and dependability of the above-mentioned analytical findings.
CONCLUSION
This study, employing MR, reveals that omeprazole, as an exposure factor, elevates the risk of OA. Considering the drug's efficacy and associated adverse events, clinical practitioners should exercise caution regarding prolonged omeprazole use, particularly in populations with heightened OA risks. Further robust and high-quality research is warranted to validate our findings and guide clinical practice.
Topics: Humans; Omeprazole; Mendelian Randomization Analysis; Osteoarthritis; United Kingdom; Biological Specimen Banks; Risk Factors; Female; Male; Middle Aged; UK Biobank
PubMed: 38802944
DOI: 10.1186/s12967-024-05255-y -
Biological & Pharmaceutical Bulletin 2024Omeprazole, a gastric acid pump inhibitor, is repeatedly administered and is oxidatively metabolized mainly by polymorphic cytochrome P450 2C19. The prescribed dosage of...
Modeled Hepatic/Plasma Exposures of Omeprazole Prescribed Alone in Cytochrome P450 2C19 Poor Metabolizers Are Likely Associated with Hepatic Toxicity Reported in a Japanese Adverse Event Database.
Omeprazole, a gastric acid pump inhibitor, is repeatedly administered and is oxidatively metabolized mainly by polymorphic cytochrome P450 2C19. The prescribed dosage of omeprazole was discontinued or reduced in 47 of the 135 patients who received omeprazole alone in this survey, as recorded in the Japanese Adverse Drug Event Report database. The days to onset of omeprazole-related disorders were 3-4 d (median) and 16 d for intravenous 20-40 mg and oral 20 mg daily doses, respectively, in 34 patients for whom relevant data were available. The maximum plasma concentration of omeprazole was pharmacokinetically modeled after a single oral 40-mg dose in P450 2C19-defective poor metabolizers and was 2.4-fold higher than that in extensive metabolizers. The modeled area under the hepatic concentration curves of omeprazole in P450 2C19 poor metabolizers after virtual daily 40-mg doses for 7 d was 5.2-fold higher than that in the extensive metabolizers. Omeprazole-induced P450 2C19 (approx. 2-fold), resulting in increased hepatic intrinsic clearance in repeated doses, was considered after the second day. Virtual plasma/hepatic exposure estimated using pharmacokinetic modeling in subjects with P450 2C19 poor metabolizers indicated that these exposure levels virtually estimated could be one of causal factors for unexpected hepatic disorders induced by prescribed omeprazole, such as those resulting from drug interactions with repeatedly co-administered medicines.
Topics: Humans; Adverse Drug Reaction Reporting Systems; Chemical and Drug Induced Liver Injury; Cytochrome P-450 CYP2C19; Databases, Factual; East Asian People; Japan; Liver; Models, Biological; Omeprazole; Proton Pump Inhibitors
PubMed: 38797695
DOI: 10.1248/bpb.b24-00145 -
Regulatory Toxicology and Pharmacology... Jun 2024Permitted Daily Exposure Limits (PDEs) are set for Active Pharmaceutical Ingredients (APIs) to control cross-contamination when manufacturing medicinal products in... (Comparative Study)
Comparative Study
Permitted Daily Exposure Limits (PDEs) are set for Active Pharmaceutical Ingredients (APIs) to control cross-contamination when manufacturing medicinal products in shared facilities. With the lack of official PDE lists for pharmaceuticals, PDEs have to be set by each company separately. Although general rules and guidelines for the setting of PDEs exist, inter-company variations in the setting of PDEs occur and are considered acceptable within a certain range. To evaluate the robustness of the PDE approach between different pharmaceutical companies, data on PDE setting of five marketed APIs (amlodipine, hydrochlorothiazide, metformin, morphine, and omeprazole) were collected and compared. Findings show that the variability between PDE values is within acceptable ranges (below 10-fold) for all compounds, with the highest difference for morphine due to different Point of Departures (PODs) and Adjustment Factors (AFs). Factors of PDE variability identified and further discussed are: (1) availability of data, (2) selection of POD, (3) assignment of AFs, (4) route-to-route extrapolation, and (5) expert judgement and differences in company policies. We conclude that the investigated PDE methods and calculations are robust and scientifically defensible. Additionally, we provide further recommendations to harmonize PDE calculation approaches across the pharmaceutical industry.
Topics: Humans; Drug Industry; Pharmaceutical Preparations; Risk Assessment; Drug Contamination; Occupational Exposure; Bulk Drugs
PubMed: 38782234
DOI: 10.1016/j.yrtph.2024.105649 -
Frontiers in Veterinary Science 2024Overprescribing of acid suppressants is a common phenomenon in human and small animal patients, leading to potential deleterious gastrointestinal (GI) and non-GI...
Prevalence and appropriateness of omeprazole prescription in dogs at a veterinary teaching hospital before and after the publication of the ACVIM consensus statement on the rational administration of gastrointestinal protectants.
INTRODUCTION
Overprescribing of acid suppressants is a common phenomenon in human and small animal patients, leading to potential deleterious gastrointestinal (GI) and non-GI consequences. The impact of consensus statements on veterinary prescribing habits in clinical practice have not been fully evaluated. This study aimed to compare the prescribing habits of the proton pump inhibitor (PPI), omeprazole, in dogs in an academic veterinary teaching hospital before and after the publication of the American College of Veterinary Internal Medicine (ACVIM) consensus statement on rational use of gastrointestinal protectants.
METHODS
Evaluation of the prescribing habits of omeprazole in dogs during the years 2017 and 2021 was retrospectively compared. These years were selected to reflect a 12-month period prior to and following the publication of the consensus statement. One hundred dogs from each year were randomly selected. Dose, frequency of administration, duration of treatment, concurrent prescription of more than one gastroprotectant and indications for prescribing omeprazole were analyzed.
RESULTS
A significant increase in the cases that received omeprazole q12h ( < 0.0001) or that underwent a tapering dose after ≥4 week-therapy ( > 0.0001) was detected after the publication of the 2018 ACVIM consensus statement. Considering the indications, there was also a significant increase in the appropriate prescription of omeprazole in the second compared to the first period of study ( < 0.0001). Fifteen of 16 clinicians (94%) involved in the prescription of omeprazole indicated that their reading of the consensus statement had changed their clinical practice regarding PPI administration in dogs.
DISCUSSION
These results support the beneficial impact of the ACVIM consensus statement on the judicious prescribing of omeprazole in an academic veterinary hospital. These results should not be extrapolated to first-opinion veterinary practices, and further efforts should be made to ensure that PPIs are prescribed prudently with a clear indication and regular review of the appropriateness of continued administration to minimize possible risks and adverse drug interactions.
PubMed: 38774912
DOI: 10.3389/fvets.2024.1352496 -
Pharmacoepidemiology and Drug Safety Jun 2024Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after...
BACKGROUND
Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs.
METHODS
We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test.
RESULTS
From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users.
CONCLUSIONS
Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.
Topics: Humans; Clopidogrel; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Male; Female; Aged; Middle Aged; Gastrointestinal Hemorrhage; Dual Anti-Platelet Therapy; Esomeprazole; Omeprazole; Drug Interactions; Drug Therapy, Combination; Histamine H2 Antagonists
PubMed: 38773801
DOI: 10.1002/pds.5816 -
Journal of Voice : Official Journal of... May 2024To investigate the correlation between dry eye disease (DED) and laryngopharyngeal reflux (LPR) from the perspective of treatment response.
OBJECTIVE
To investigate the correlation between dry eye disease (DED) and laryngopharyngeal reflux (LPR) from the perspective of treatment response.
STUDY DESIGN
Cross-sectional studies.
SETTING
Analysis of data from patients with DED-related symptoms and LPR-related symptoms from May 2022 to January 2023 at AIER Eye Hospital (Hainan).
METHODS
The Ocular Surface Symptom Index (OSDI) scales and The Reflux Symptom Score (RSS) were investigated in patients attending China Aier Eye Hospital (Hainan) from May 2022 to January 2023, and OSDI scores >12 were categorized as DED, and RSS scores >13 were categorized as suspected laryngopharyngeal reflux (suspected LPR). Patients with DED and suspected LPR were randomly divided into three groups (group A: 0.3% sodium vitreous acid drops and 1% cyclosporine A drops only; group B: 0.3% sodium vitreous acid drops, 1% cyclosporine A drops, and Gastroftal tablets containing magnesium alginate and cimicifuga oil and esomeprazole; and group C: Gastroftal tablets and esomeprazole only orally) and were reviewed after 3 months for the RSS- and DED-related examinations.
RESULT
Two hundred and nineteen patients were enrolled. One hundred and ninety-one DED-positive and 28 DED-negative patients, 84 suspected LPR-positive and 135 LPR-negative patients, and the OSDI scores of LPR patients were significantly higher than those of LPR-negative patients (P < 0.001). Parameters related to DED and LPR were significantly lower in patients in group B than in groups A and C after treatment (P < 0.001).
CONCLUSIONS
LPR and DED are closely related. For patients with both LPR and DED, treating LPR and DED at the same time may be a better option.
PubMed: 38763849
DOI: 10.1016/j.jvoice.2024.04.023 -
Journal of the American Pharmacists... May 2024ChatGPT is a conversational artificial intelligence technology that has shown application in various facets of healthcare. With the increased use of AI, it is imperative...
BACKGROUND
ChatGPT is a conversational artificial intelligence technology that has shown application in various facets of healthcare. With the increased use of AI, it is imperative to assess the accuracy and comprehensibility of AI platforms.
OBJECTIVE
This pilot project aimed to assess the understandability, readability, and accuracy of ChatGPT as a source of medication-related patient education as compared with an evidence-based medicine tertiary reference resource, LexiComp®.
METHODS
Patient education materials (PEMs) were obtained from ChatGPT and LexiComp® for 8 common medications (albuterol, apixaban, atorvastatin, hydrocodone/acetaminophen, insulin glargine, levofloxacin, omeprazole, and sacubitril/valsartan). PEMs were extracted, blinded, and assessed by 2 investigators independently. The primary outcome was a comparison of the Patient Education Materials Assessment Tool-printable (PEMAT-P). Secondary outcomes included Flesch reading ease, Flesch Kincaid grade level, percent passive sentences, word count, and accuracy. A 7-item accuracy checklist for each medication was generated by expert consensus among pharmacist investigators, with LexiComp® PEMs serving as the control. PEMAT-P interrater reliability was determined via intraclass correlation coefficient (ICC). Flesch reading ease, Flesch Kincaid grade level, percent passive sentences, and word count were calculated by Microsoft® Word®. Continuous data were assessed using the Student's t-test via SPSS (version 20.0).
RESULTS
No difference was found in the PEMAT-P understandability score of PEMs produced by ChatGPT versus LexiComp® [77.9% (11.0) vs. 72.5% (2.4), P=0.193]. Reading level was higher with ChatGPT [8.6 (1.2) vs. 5.6 (0.3), P < 0.001). ChatGPT PEMs had a lower percentage of passive sentences and lower word count. The average accuracy score of ChatGPT PEMs was 4.25/7 (61%), with scores ranging from 29% to 86%.
CONCLUSION
Despite comparable PEMAT-P scores, ChatGPT PEMs did not meet grade level targets. Lower word count and passive text with ChatGPT PEMs could benefit patients, but the variable accuracy scores prevent routine use of ChatGPT to produce medication-related PEMs at this time.
PubMed: 38729608
DOI: 10.1016/j.japh.2024.102119 -
American Journal of Veterinary Research May 2024Develop a cytochrome P450 (CYP) phenotyping cocktail for dogs using specific substrates for hepatic P450 enzymes CYP2B11, CYP2D15, and CYP3A12 and determine whether...
OBJECTIVE
Develop a cytochrome P450 (CYP) phenotyping cocktail for dogs using specific substrates for hepatic P450 enzymes CYP2B11, CYP2D15, and CYP3A12 and determine whether alternative sampling methods (saliva and urine) or single time point samples could be used instead of multiple blood sampling.
ANIMALS
12 healthy client-owned dogs (8 females and 4 males) from February 2019 to May 2019.
METHODS
In a randomized crossover study, dogs received oral administration of the probe drug bupropion (75 mg), dextromethorphan (30 mg), or omeprazole (40 mg) alone or as a 3-drug combination (Program in Individualized Medicine [PrIMe] cocktail) to evaluate simultaneous phenotyping of CYP2B11, CYP2D15, and CYP3A12. Pharmacokinetic profiles for the probe drugs and metabolites were determined using plasma, saliva, and urine. Dogs received probe drugs alone or combined. Pharmacokinetic profiles up to 6 hours postdose for the probe drugs and metabolites were determined using plasma, saliva, and urine.
RESULTS
The PrIMe cocktail was well tolerated. There was no statistically significant interaction between the probe drugs when administered together. Single time point plasma metabolic ratios at 4 hours postdose for all probe drugs strongly correlated with the corresponding area under the plasma concentration-versus-time curve (AUC) ratios. Saliva AUC metabolic ratios for CYP3A12 and CYP2D15 and 6-hour urine for CYP2B11 and CYP2D15 were correlated with plasma AUC ratios.
CONCLUSIONS
The PrIMe cocktail can be used for simultaneous CYP phenotyping using plasma 4-hour single time point sample metabolic ratios. Saliva and urine sampling are suitable for specific CYPs.
CLINICAL RELEVANCE
The PrIMe cocktail has potential as a useful tool in dogs to detect clinically important CYP-mediated drug-drug interactions, identify novel pharmacogenes, determine the drug-metabolizing phenotype of individual dogs, aid in individualized dose selection, and evaluate the effects of various physiological states on drug metabolism.
PubMed: 38718826
DOI: 10.2460/ajvr.24.02.0049 -
Acta Cirurgica Brasileira 2024Reflux esophagitis is a condition characterized by inflammation and irritation of the esophagus, resulting from the backflow of stomach acid and other gastric contents...
PURPOSE
Reflux esophagitis is a condition characterized by inflammation and irritation of the esophagus, resulting from the backflow of stomach acid and other gastric contents into the esophagus. Columbianadin is a coumarin derivative that exhibits anti-inflammatory and antioxidant effects. In this study, we tried to scrutinize the protective effect of Columbianadin against acute reflux esophagitis in rats.
METHODS
RAW 264.7 cells were utilized to assess cell viability and measure the production of inflammatory parameters. The rats received anesthesia, and reflux esophagitis was induced via ligation of pylorus and fore stomach and corpus junction. Rats received the oral administration of Columbianadin (25, 50 and 100 mg/kg) and omeprazole (20 mg/kg). The gastric secretion volume, acidity, and pH were measured. Additionally, the levels of oxidative stress parameters, cytokines, and inflammatory markers were determined. At the end of the study, mRNA expression was assessed.
RESULTS
Columbianadin remarkably suppressed the cell viability and production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and prostaglandin (PGE2). Columbianadin treatment remarkably suppressed the secretion of gastric volume, total acidity and enhanced the pH level in the stomach. Columbianadin remarkably altered the level of hydrogen peroxidase, free iron, calcium, and plasma scavenging activity, sulfhydryl group; oxidative stress parameters like malonaldehyde, glutathione, superoxide dismutase, catalase, glutathione peroxidase; inflammatory cytokines viz., TNF-α, IL-6, IL-1β, IL-10, IL-17, and monocyte chemoattractant protein-1; inflammatory parameters including PGE2, iNOS, COX-2, and nuclear kappa B factor (NF-κB). Columbianadin remarkably (P < 0.001) suppressed the mRNA expression TNF-α, IL-6, IL-1β and plasminogen activator inhibitor-1.
CONCLUSIONS
Columbianadin demonstrated a protective effect against acute reflux esophagitis via NF-κB pathway.
Topics: Animals; Esophagitis, Peptic; NF-kappa B; Male; Rats; Oxidative Stress; Cytokines; Disease Models, Animal; Cell Survival; Acute Disease; RAW 264.7 Cells; Mice; Rats, Wistar; Signal Transduction; Antioxidants; Anti-Inflammatory Agents
PubMed: 38716957
DOI: 10.1590/acb391824