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Frontiers in Medicine 2022Proton pump inhibitors (PPIs) are acid suppressants that are frequently prescribed in many countries to reduce heartburn. A potassium-competitive acid blocker (P-CAB;...
BACKGROUND
Proton pump inhibitors (PPIs) are acid suppressants that are frequently prescribed in many countries to reduce heartburn. A potassium-competitive acid blocker (P-CAB; tegoprazan) was launched relatively recently that also inhibits gastric acid secretion. This study aimed to compare the hepatotoxicity of the six existing PPIs with P-CAB.
METHODS
This retrospective cohort study was conducted between January 2019 and December 2020 and included data from the total population of 50 million inhabitants in Korea. Propensity score (PS) matching was performed using 10 variables, and the differences in hepatotoxicity between P-CAB and the six PPIs were compared in a similar distribution. The primary endpoint was hepatotoxicity which included toxic liver disease, hepatitis, hepatic failure, liver transplantation, and other liver diseases.
RESULTS
The risk ratios (RR) of tegoprazan vs. the six PPIs (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) were all significant [RR: 0.70 (95% CI: 0.69-0.72), 0.81 (95% CI: 0.79-0.83), 0.61 (95% CI: 0.59-0.63), 1.17 (95% CI: 1.13-1.20), 0.61 (95% CI: 0.59-0.62), and 0.73 (95% CI: 0.71-0.75), respectively]. The risk ratio of tegoprazan vs. the six existing PPIs was 0.73 (95% CI: 0.72-0.75). The hazard ratios (HRs) of hepatotoxicity of the six PPIs to tegoprazan showed significantly higher values apart from omeprazole (HR: dexlansoprazole, 1.13; esomeprazole, 1.04; lansoprazole, 1.25; omeprazole, 0.77; pantoprazole, 1.26; rabeprazole, 1.15, respectively, and the six existing PPIs, 1.10).
CONCLUSION
Using a large-scale data cohort analysis consisting of 50 million Koreans, tegoprazan did not induce higher hepatotoxicity compared with the six conventional PPIs.
PubMed: 36714137
DOI: 10.3389/fmed.2022.1076356 -
Scientific Reports Dec 2020Proton pump inhibitors (PPIs) belong to the most common medication in geriatric medicine. They are known to reduce osteoclast activity and to delay fracture healing in...
Proton pump inhibitors (PPIs) belong to the most common medication in geriatric medicine. They are known to reduce osteoclast activity and to delay fracture healing in young adult mice. Because differentiation and proliferation in fracture healing as well as pharmacologic actions of drugs markedly differ in the elderly compared to the young, we herein studied the effect of the PPI pantoprazole on bone healing in aged mice using a murine fracture model. Bone healing was analyzed by biomechanical, histomorphometric, radiological and protein biochemical analyses. The biomechanical analysis revealed a significantly reduced bending stiffness in pantoprazole-treated animals when compared to controls. This was associated with a decreased amount of bone tissue within the callus, a reduced trabecular thickness and a higher amount of fibrous tissue. Furthermore, the number of osteoclasts in pantoprazole-treated animals was significantly increased at 2 weeks and decreased at 5 weeks after fracture, indicating an acceleration of bone turnover. Western blot analysis showed a lower expression of the bone morphogenetic protein-4 (BMP-4), whereas the expression of the pro-angiogenic parameters was higher when compared to controls. Thus, pantoprazole impairs fracture healing in aged mice by affecting angiogenic and osteogenic growth factor expression, osteoclast activity and bone formation.
Topics: Aging; Animals; Bone Morphogenetic Protein 4; Disease Models, Animal; Fracture Healing; Mice; Neovascularization, Physiologic; Osteogenesis; Pantoprazole
PubMed: 33361800
DOI: 10.1038/s41598-020-79605-3 -
European Journal of Case Reports in... 2021Drugs can cause fever of unknown origin. Drug fever is a diagnosis of exclusion and can lead to unnecessary investigations and prolonged hospitalization. Any drug can be...
UNLABELLED
Drugs can cause fever of unknown origin. Drug fever is a diagnosis of exclusion and can lead to unnecessary investigations and prolonged hospitalization. Any drug can be responsible. Here, we describe the case of a woman admitted because of acute hepatitis. Pantoprazole was started for stress ulcer prophylaxis when she was admitted to the ICU. Fever developed a few days later and an extensive diagnostic work-up was negative. Fever remitted after pantoprazole discontinuation and the diagnosis of drug fever was established.
LEARNING POINTS
Despite extensive diagnostic work-up, the aetiology of acute liver failure remains unclear in a large proportion of cases.Drug fever is a diagnosis of exclusion and must be considered in every patient with unexplained fever; any drug should be seen as a possible offending agent.Pantoprazole, a commonly prescribed drug, can be a rare cause of fever.
PubMed: 34123946
DOI: 10.12890/2021_002571 -
Journal of Research in Pharmacy Practice 2021Gastrointestinal bleeding, a side effect of clopidogrel, is usually prevented by proton-pump inhibitors (PPIs). Due to omeprazole's inhibitory effects on the liver...
Cost-Effectiveness and Cost-Utility Analysis of the Use of Clopidogrel and Pantoprazole in Comparison with Clopidogrel and Omeprazole for the Secondary Prevention of Myocardial Infarction in Iran.
OBJECTIVE
Gastrointestinal bleeding, a side effect of clopidogrel, is usually prevented by proton-pump inhibitors (PPIs). Due to omeprazole's inhibitory effects on the liver enzyme CYP2C19, its concomitant use with clopidogrel is argued to increase the risk of myocardial infarction (MI) recurrence, as CYP2C19 activates clopidogrel. Pantoprazole as an alternative PPI has shown no inhibitory effect on CYP2C19. This study investigates the cost-effectiveness of concomitant use of clopidogrel and pantoprazole in MI patients compared to the simultaneous use of clopidogrel and omeprazole.
METHODS
We used the Markov-modeling technique with a hypothetical cohort of 1000 acute MI patients aged 55 years using Microsoft Excel 2013 software. The study was done from the payer perspective, and a lifetime horizon with 1-year cycles was considered in the model. Life-years gained (LYG) and quality-adjusted life-years (QALYs) were used to quantify the health effects of these interventions. Two separate scenarios of public tariffs and private tariffs with various discount rates (0%, 3%, and 7.2% discounts (only for costs)) were evaluated, and an incremental cost-effectiveness ratio (ICER) was used to report the results. One-way and probabilistic sensitivity analyses were used to deal with uncertainty. Data were sourced from published literature and tariff book of the Iranian ministry of health.
FINDINGS
The estimated ICERs were 342 USD/QALY and 236 USD/LYG per patient for the base-case scenario.
CONCLUSION
Abiding by the WHO threshold for cost-effectiveness, the concomitant use of pantoprazole and clopidogrel can be considered cost-effective compared to the use of omeprazole and clopidogrel.
PubMed: 34527614
DOI: 10.4103/jrpp.JRPP_21_22 -
World Journal of Gastroenterology Nov 2021The use of proton pump inhibitors (PPI) is common worldwide, with reports suggesting that they may be overused. Several studies have found that PPI may affect colorectal...
BACKGROUND
The use of proton pump inhibitors (PPI) is common worldwide, with reports suggesting that they may be overused. Several studies have found that PPI may affect colorectal cancer (CRC) risk.
AIM
To summarize current knowledge on the relationship between PPI and CRC from basic research, epidemiological and clinical studies.
METHODS
This systematic review was based on the patients, interventions, comparisons, outcome models and performed according to PRISMA guidelines. MEDLINE, EMBASE, Scopus, and Web of Science databases were searched from inception until May 17, 2021. The initial search returned 2591 articles, of which, 28 studies met the inclusion criteria for this review. The studies were categorized as basic research studies ( = 12), epidemiological studies ( = 11), and CRC treatment studies ( = 5). The quality of the included studies was assessed using the Newcastle-Ottawa Scale or Cochrane Risk of Bias 2.0 tool depending on the study design.
RESULTS
Data from basic research indicates that PPI do not stimulate CRC development the trophic effect of gastrin but instead may paradoxically inhibit it. These studies also suggest that PPI may have properties beneficial for CRC treatment. PPI appear to have anti-tumor properties (omeprazole, pantoprazole), and are potential T lymphokine-activated killer cell-originated protein kinase inhibitors (pantoprazole, ilaprazole), and chemosensitizing agents (pantoprazole). However, these mechanisms have not been confirmed in human trials. Current epidemiological studies suggest that there is no causal association between PPI use and increased CRC risk. Treatment studies show that concomitant PPI and capecitabine use may reduce the efficacy of chemotherapy resulting in poorer oncological outcomes, while also suggesting that pantoprazole may have a chemosensitizing effect with the fluorouracil, leucovorin, oxaliplatin (FOLFOX) regimen.
CONCLUSION
An unexpected inhibitory effect of PPI on CRC carcinogenesis by way of several potential mechanisms is noted. This review identifies that different PPI agents may have differential effects on CRC treatment, with practical implications. Prospective studies are warranted to delineate this relationship and assess the role of individual PPI agents.
Topics: Capecitabine; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Proton Pump Inhibitors
PubMed: 34908809
DOI: 10.3748/wjg.v27.i44.7716 -
Scientific Reports May 2022Knowing the solubility data of pharmaceutical compounds in supercritical carbon dioxide (ScCO) is essential for nanoparticles formation by using supercritical...
Knowing the solubility data of pharmaceutical compounds in supercritical carbon dioxide (ScCO) is essential for nanoparticles formation by using supercritical technology. In this work, solubility of solid pantoprazole sodium sesquihydrate in ScCO is determined and reported at 308, 318, 328 and 338 K and at pressures between 12 and 27 MPa. The solubilities are ranged between 0.0301 [Formula: see text] 10 and 0.463 [Formula: see text] 10 in mole fraction. The determined solubilities are modelled with a new model using solid-liquid equilibrium criteria and the required activity coefficient is developed using regular solution theory. The measured solubilities data are also modelled with three recent and four conventional empirical models. The recent models used are, Alwi-Garlapati (AARD = 13.1%), Sodeifian et al. (14.7%), and Tippana-Garlapati (15.5%) models and the conventional models used are Chrastil (17.54%), reformulated Chrastil (16.30%), Bartle (14.1%) and Mendenz Santiago and Teja (MT) (14.9%) models. The proposed model is correlating the data with less than 14.9% and 16.23% in terms of AARD for temperature dependent and independent cases. Among exiting models, Mendez Santiago and Teja (MT) and Alwi-Garlapati models correlate the data better than other models (corresponding AARD% and AIC are 14.9, 13.1 and -518.89, -504.14, respectively). The correlation effectiveness of the models is evaluated in terms of Corrected Akaike's Information Criterion (AIC). Finally, enthalpy of solvation and vaporization of pantoprazole sodium sesquihydrate are calculated and reported. The new model proposed in this study can be used for the combination of any complex compound with any supercritical fluid.
Topics: Carbon Dioxide; Pantoprazole; Solubility; Temperature; Thermodynamics
PubMed: 35546179
DOI: 10.1038/s41598-022-11887-1 -
International Journal of Environmental... Mar 2021Proton pump inhibitors (PPIs) are the first-choice drugs used to prevent and treat acid-related diseases. However, a lack of satisfactory response to the standard PPI... (Review)
Review
Proton pump inhibitors (PPIs) are the first-choice drugs used to prevent and treat acid-related diseases. However, a lack of satisfactory response to the standard PPI dose ("PPI failure") is often reported, especially in patients with gastroesophageal reflux disease. Poor compliance seems to be one of the main causes of PPI failure; hence, it is crucial to gain knowledge on how to properly administer PPIs. In this review, we aimed to evaluate the effect of food, beverages, and dosing regimen on pharmacokinetics and pharmacodynamics of PPIs and to frame recommendations for healthcare professionals to improve both patient's counseling and compliance to treatment with PPIs. A total of 201 papers were identified following a literature search. After full-text evaluation, 64 studies were included in the review. Co-administration of PPIs with a meal may affect both their bioavailability and effectiveness; however, the influence of food depends on the type of drug and its formulation. Except for pantoprazole, PPIs can be administered in the morning or evening; however, morning intake generally provides better daytime control of gastric acidity. In most cases, the choice of the proper schedule of administration should be based on the patient's symptoms and individual dosing preferences.
Topics: Clinical Protocols; Food; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors
PubMed: 33805341
DOI: 10.3390/ijerph18073527 -
American Journal of Translational... 2021To investigate the protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats.
OBJECTIVE
To investigate the protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats.
METHODS
Healthy, specifically pathogen free SD, rats were selected and divided into 4 groups: Normal group (normal rats, without any treatment), Model group (rats received dual antiplatelet therapy: aspirin and clopidogrel), Teprenone group (rats received dual antiplatelet therapy and teprenone) and Pantoprazole group (rats received dual antiplatelet therapy and pantoprazole). The gastric mucosal blood flow, ulcer index, gastric gel mucus thickness, the levels of gastrin (Gas), prostaglandin (PG), prostaglandin E (PGE), endothelin-1 (ET-1) tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 in serum, the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and myeloperoxidase (MPO) in the gastric mucosa, as well as the expression of vascular endothelial growth factor (VEGF) in the rat's stomach were measured.
RESULTS
Compared with the Normal group, the other groups showed more severe gastric injury, elevated levels of inflammatory factors (TNF-α, IL-1β, IL-6 and IL-10), elevated levels of MDA and MPO, as well as reduced levels of GSH, SOD and VEGF (all P<0.05). Compared with the Model group, the gastric mucosal lesions in the Teprenone group and the Pantoprazole group were improved significantly (both P<0.05). Compared with the Pantoprazole group, the Teprenone group had reduced levels of ET-1 and elevated levels of PG and PGE (all P<0.05).
CONCLUSION
Teprenone protects against gastric mucosal injury induced by dual antiplatelet therapy through inhibiting gastric mucosal inflammation inhibiting oxidative stress and improving gastric mucosa indices.
PubMed: 34017431
DOI: No ID Found -
Pharmacological Research Jun 2024Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6... (Review)
Review
Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), a vital component of the Wnt signaling pathway, has emerged as an intriguing candidate. As a cell-surface receptor and vital co-receptor, LRP6 is frequently overexpressed in various cancer types, implicating its pivotal role in driving tumor progression. The pursuit of LRP6 as a target for cancer treatment has gained substantial traction, offering a promising avenue for therapeutic intervention. Here, this comprehensive review explores recent breakthroughs in our understanding of LRP6's functions and underlying molecular mechanisms, providing a profound discussion of its involvement in cancer pathogenesis and drug resistance. Importantly, we go beyond discussing LRP6's role in cancer by discussing diverse potential therapeutic approaches targeting this enigmatic protein. These approaches encompass a wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, and peptides that modulate LRP6 expression or disrupt its interactions. In addition, also discussed the challenges associated with developing LRP6 inhibitors and their advantages over Wnt inhibitors, as well as the drugs that have entered phase II clinical trials. By shedding light on these innovative strategies, we aim to underscore LRP6's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.
Topics: Humans; Low Density Lipoprotein Receptor-Related Protein-6; Neoplasms; Animals; Antineoplastic Agents; Molecular Targeted Therapy; Wnt Signaling Pathway
PubMed: 38710241
DOI: 10.1016/j.phrs.2024.107200 -
Medicine Dec 2021Data are conflicting on whether proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel. We investigated individual PPIs and adverse cardiovascular events in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Data are conflicting on whether proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel. We investigated individual PPIs and adverse cardiovascular events in postpercutaneous coronary intervention (PCI) patients on dual antiplatelet therapy with clopidogrel.
METHODS
We searched Ovid-MEDLINE, EMBASE, and Cochrane from inception to March 2020 to identify studies that evaluated the efficacy and safety of clopidogrel added PPIs versus clopidogrel only in post-PCI patient. We extracted data from 28 studies for major adverse cardiovascular endpoints (MACE), myocardial infarction (MI), cardiovascular death, and gastrointestinal bleeding. Risk ratios (RR) and hazard ratios (HR) were pooled separately.
RESULTS
Data were extracted on 131,412 patients from the 28 studies included. Concomitant use of PPI with clopidogrel was associated with increased risk of MACE (RR 1.30; 95% confidence interval [CI] 1.15-1.48; P < .001) and MI (RR 1.43; 95% CI 1.25-1.64; P < .001). Random-effects meta-analyses with individual PPIs demonstrated an increased risk of MACE in those taking pantoprazole (RR 1.31; 95% CI 1.07-1.61, P = .01) or lansoprazole (RR 1.35; 95% CI 1.19-1.54, P < .0001) compared with patients not on PPIs. Likewise, in adjusted analyses, the pooled HR of adjusted events for MACEs showed that the increased risk of MACEs was similar for 4 classes of PPIs but not for rabeprazole (HR: 1.32; 95% CI 0.69-2.53, P = .40).
CONCLUSION
The post-PCI patients on dual antiplatelet therapy with clopidogrel in the PPI group were associated with higher risk of MACE and MI. Although the results for rabeprazole were not robust, it was the only PPI that did not yield a significantly increased risk of MACE.
Topics: Clopidogrel; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Rabeprazole; Ticlopidine; Treatment Outcome
PubMed: 34967346
DOI: 10.1097/MD.0000000000027411