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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 -
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 -
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 -
ACS Applied Materials & Interfaces May 2024Metal-organic frameworks (MOFs), which are composed of crystalline microporous materials with metal ions, have gained considerable interest as promising substrate...
Metal-organic frameworks (MOFs), which are composed of crystalline microporous materials with metal ions, have gained considerable interest as promising substrate materials for surface-enhanced Raman scattering (SERS) detection via charge transfer. Research on MOF-based SERS substrates has advanced rapidly because of the MOFs' excellent structural tunability, functionalizable pore interiors, and ultrahigh surface-to-volume ratios. Compared with traditional noble metal SERS plasmons, MOFs exhibit better biocompatibility, ease of operation, and tailorability. However, MOFs cannot produce a sufficient limit of detection (LOD) for ultrasensitive detection, and therefore, developing an ultrasensitive MOF-based SERS substrate is imperative. To the best of our knowledge, this is the first study to develop an MOFs/heterojunction structure as an SERS enhancing material. We report an ZIF-67/Co(OH) heterojunction-based nanocellulose paper (nanopaper) plate ( ZIF-67 nanoplate) as a device with an LOD of 0.98 nmol/L for Rhodamine 6G and a Raman enhancement of 1.43 × 10, which is 100 times better than that of the pure ZIF-67-based SERS substrate. Further, we extend this structure to other types of MOFs and develop an HKUST-1 nanoplate (with HKUST-1/Cu(OH)). In addition, we demonstrate that the formation of heterojunctions facilitates efficient photoinduced charge transfer for SERS detection by applying the M(OH)-assisted (where M = Co, Cu, or other metals) MOFs/heterojunction structure. Finally, we successfully demonstrate the application of medicine screening on our nanoplates, specifically for omeprazole. The nanoplates we developed still maintain the tailorability of MOFs and perform high anti-interference ability. Our approach provides customizing options for MOF-based SERS detection, catering to diverse possibilities in future research and applications.
PubMed: 38716706
DOI: 10.1021/acsami.4c01588 -
Clinical and Translational Science May 2024St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and...
St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P-gp activity at the human blood-brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)-targeted P-gp substrate drugs. In this study, we used a combination of positron emission tomography (PET) imaging and cocktail phenotyping to gain a comprehensive picture on the effect of SJW on central and peripheral P-gp and CYP activities. Before and after treatment of healthy volunteers (n = 10) with SJW extract with a high hyperforin content (3-6%) for 12-19 days (1800 mg/day), the activity of P-gp at the BBB was assessed by means of PET imaging with the P-gp substrate [C]metoclopramide and the activity of peripheral P-gp and CYPs was assessed by administering a low-dose phenotyping cocktail (caffeine, omeprazole, dextromethorphan, and midazolam or fexofenadine). SJW significantly increased peripheral P-gp, CYP3A, and CYP2C19 activity. Conversely, no significant changes in the peripheral metabolism, brain distribution, and P-gp-mediated efflux of [C]metoclopramide across the BBB were observed following the treatment with SJW extract. Our data suggest that SJW does not lead to significant P-gp induction at the human BBB despite its ability to induce peripheral P-gp and CYPs. Simultaneous intake of SJW with CNS-targeted P-gp substrate drugs is not expected to lead to P-gp-mediated drug interactions at the BBB.
Topics: Humans; Hypericum; Blood-Brain Barrier; Phloroglucinol; Plant Extracts; Male; Adult; Positron-Emission Tomography; Terpenes; Female; Young Adult; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily B; Bridged Bicyclo Compounds; Terfenadine; Cytochrome P-450 Enzyme System; Healthy Volunteers
PubMed: 38700454
DOI: 10.1111/cts.13804 -
JGH Open : An Open Access Journal of... May 2024To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for () treatment.
BACKGROUND AND AIM
To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for () treatment.
METHODS
From August 2022 to May 2023, clinical data were collected from patients who received eradication treatment at West China Fourth Hospital, Sichuan University. One group received the MVAB regimen (amoxicillin, minocycline, vonoprazan, and colloidal bismuth pectin), while another group received the FOAB regimen (amoxicillin, furazolidone, omeprazole, and colloidal bismuth pectin), both administered for 14 days. Follow-up assessments of safety and compliance were conducted within 1 week after treatment completion. One and a half months after treatment, the success of eradication was evaluated using the urea breath test.
RESULTS
For the MVAB regimen as a first-line treatment, the eradication rate was 90.1% (127/141, 95% CI: 85.1-95.1%) in the ITT analysis and 93.4% (127/136, 95% CI: 89.2-97.6%) in the PP analysis as a first-line treatment. As a second-line treatment, the eradication rate was 91.3% (21/23, 95% CI: 78.8-103.8%) in both analyses. For the FOAB regimen as a first-line treatment, the eradication rate was 98.0% (50/51, 95% CI: 94.1-101.2%) in the ITT analysis and 100% (50/50, 95% CI: 100%) in the PP analysis. As a second-line treatment, the eradication rate was 100% (6/6, 95% CI: 100%) in both analyses. Moreover, there was no significant difference in the incidence of adverse events between the two groups (MVAB regimen: 5.5% and FOAB regimen: 8.8%; > 0.05).
CONCLUSIONS
The MVAB regimen could indeed be a viable alternative treatment option to conventional therapies.
PubMed: 38699469
DOI: 10.1002/jgh3.13070 -
In Vivo (Athens, Greece) 2024Recent research has increasingly demonstrated an association between proton pump inhibitors (PPIs) and serious adverse events. This study aimed to evaluate the...
BACKGROUND/AIM
Recent research has increasingly demonstrated an association between proton pump inhibitors (PPIs) and serious adverse events. This study aimed to evaluate the association between PPI and rhabdomyolysis (RM), examining its time-to-onset profiles using the Japanese Adverse Drug Event Report (JADER) database.
PATIENTS AND METHODS
Data spanning from April 2004 to March 2022 were used. The association between PPIs and RM was evaluated using the reporting odds ratio (ROR), adjusted for sex and age. Subsequent analyses were conducted after excluding cases involving concomitant use of statins or fibrates. Furthermore, the onset time of RM and Weibull distribution parameters were calculated to evaluate the expression profile of RM, and the outcomes were examined.
RESULTS
RM was associated with the use of esomeprazole, omeprazole, and rabeprazole, even in the absence of concomitant statin or fibrate use. The median time to RM onset varied among PPIs, ranging from 6.5 to 127 d. The Weibull distribution parameters indicated that the hazard types of nearly all orally administered PPIs were classified as early failure or close to random failure. Regarding outcomes, cases of death were reported for all PPIs except vonoprazan.
CONCLUSION
The findings suggest the need for vigilant monitoring of RM during PPI administration, particularly in the early stages, considering the varying onset times.
Topics: Humans; Proton Pump Inhibitors; Rhabdomyolysis; Male; Female; Pharmacovigilance; Middle Aged; Aged; Adult; Adverse Drug Reaction Reporting Systems; Databases, Factual; Aged, 80 and over; Young Adult; Adolescent; Esomeprazole
PubMed: 38688634
DOI: 10.21873/invivo.13567