Proton Pump Inhibitor Omeprazole Research Articles

Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence.

Background: Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently, concerns have been raised about their safety, particularly due to the association between long-term PPI use and cancer development. Multiple comprehensive studies have consistently suggested a noteworthy link between prolonged PPI usage and an increased risk of developing gastric, esophageal, colorectal, and pancreatic cancers, yet the precise underlying mechanism remains elusive. Methods: First, we review the extensive body of research that investigates the intricate relationship between cancer and PPIs. Then, we predict PPI toxicity using the prodrug structures with the ProTox-II webserver. Finally, we predict the relative risk of cancer for each PPI, using PubMed citation counts of each drug and keywords related to cancer. Results: Our review indicates that prolonged PPI use (exceeding three months) is significantly associated with an elevated risk of cancer, while shorter-term usage (less than three months) appears to pose a comparatively lower risk. Our review encompasses various proposed mechanisms, such as pH and microbiome alterations, vitamin and mineral malabsorption, hypergastrinemia, and enterochromaffin-like cell proliferation, while ProTox-II also suggests aryl hydrocarbon receptor binding. Potentially, the PubMed citations count suggests that the PPIs omeprazole and lansoprazole are more associated with cancer than pantoprazole and esomeprazole. In comparison, the H2R blocker, famotidine, is potentially less associated with cancer than PPIs, and may serve as a safer alternative treatment for periods beyond 3 months. Conclusions: Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management.

Greenness-sustainability metrics for assessment smart-chemometric spectrophotometric strategy for evaluation of the combination of six gastric proton-pump inhibitors with two selected impurities

Green analytical approaches are employed for the determination of active pharmaceutical ingredients, in conjunction with their impurities. Smart chemometric spectrophotometric techniques, including orthogonal partial least square (OPLS), variable selection such as genetic algorithm (GA-OPLS), and interval selection (i-OPLS), were utilized. These chemometric models were implemented for assessing six proton-pump inhibitors Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole, Rabeprazole, and Dexlansoprazole along with two selected official impurities, namely 4-Desmethoxy omeprazole impurity and Rabeprazole-impurity B. Experimental design was implemented to separate impurities, in the process of multivariate calibration, a five-level eight-factor calibration design consisting of 25 samples was selected. This design was deliberately selected to guarantee that the components were mutually orthogonal to assess the model's performance and reliability, a separate validation set of 15 samples was constructed. The best-performing of the proposed techniques were identified by considering the least favorable values of the Correlation Coefficient (R ≥ 0.9995), the Root Mean Square Error of Prediction (RMSEP) values between (0.0102–0.5622), and the Relative Error of Prediction (REP) values between (0.2961–1.1917). The proposed and reported methods' greenness-sustainability was quantitatively evaluated, and a comparative study of the greenness profile was established through a spider chart, the National Environmental Method Index tool, advanced and modified NEMI along with the Hexagon tool, and the whiteness qualities of the presented approaches were assessed by implementing the recently adopted Red-Green-Blue paradigm and White Analytical Chemistry tool. These approaches are well-suited for use in quality control laboratories due to their observed acceptance, long-term sustainability, simplicity, and affordability.

Proton Pump Inhibitors Do Not Affect the Bioavailability of a Novel Liquid Formulation of Levothyroxine

ObjectiveThis study evaluates the impact of a representative proton pump inhibitor (PPI) (omeprazole), administered simultaneously or staggered, on the pharmacokinetics of levothyroxine (LT4) solution (Tirosint-SOL). MethodsThis was a randomized, 3-way crossover, comparative bioavailability study in 36 healthy adults under fasting conditions.Omeprazole 40 mg delayed-release capsule was administered once daily from Day 1 to 6 (mornings, Treatment-A; evenings, Treatment-B; none, Treatment-C) to increase and stabilize gastric pH. In the morning of Day 5, a single dose of LT4 solution 600 mcg was administered. Blood samples were collected 0 to 48 hours post-LT4 administration. Noncompartmental pharmacokinetic parameters were calculated for total serum thyroxine using baseline-corrected data. Maximum concentration (Cmax) and area under the concentration-time curve (AUC0-48) were included in an analysis of variance to obtain geometric mean ratios and 90% confidence intervals. ResultsFor both comparisons (A/C and B/C), geometric mean ratios and 90% confidence intervals for all parameters were within the equivalence boundaries (80%-125%), indicating bioequivalence: for A/C, AUC0-48 98.98% [94%-104%], and Cmax 91.68% [87%-97%]; for B/C, AUC0-48 98.94% [95%-103%], and Cmax 94.90% [90%-100%]. Median Tmax (time associated with Cmax) was similar across treatments. ConclusionThis study demonstrated that Tirosint-SOL bioavailability is unaffected by coadministration of a representative PPI, given simultaneously or staggered by about 12 hours, compared to administration of LT4 solution alone. For hypothyroid patients on PPI therapy, administration of LT4 solution may reduce variations in thyroid stimulating hormone levels related to intermittent use of acid-reducing drugs and consequently the need for dose adjustments.

Equine gastric ulcer syndrome in horses and foals

Gastric ulcers are common in adult horses and can also be present in foals. It is important to realise that ulcers can occur in the squamous and/or glandular mucosa of the stomach, and that these represent two different disease entities, namely equine squamous gastric disease and equine glandular gastric disease. Horses suspected of having gastric ulcers based on clinical signs should undergo gastroscopy to confirm the presence of ulcers and determine their severity, although there is a poor correlation between gastroscopic findings and clinical severity. As both squamous and glandular gastric disease are the result of tissue damage caused by gastric acid, the proton pump inhibitor omeprazole forms the mainstay of ulcer treatment. In cases of glandular gastric disease, sucralfate is usually added to the therapeutic plan. As several husbandry and management practices are known to be risk factors for the development of ulcers, these should be addressed during treatment and to prevent recurrence.

Inhibitors of gastric acid secretion increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling.

The use of inhibitors of gastric acid secretion (IGAS), especially proton pump inhibitors (PPI), has been associated with increased cardiovascular risk. While the mechanisms involved are not known, there is evidence supporting increased oxidative stress, a major activator of matrix metalloproteinases (MMP), as an important player in such effect. However, there is no study showing whether other IGAS such as histamine H2-receptor blockers (H2RB) cause similar effects. This study aimed at examining whether treatment with the H2RB ranitidine promotes oxidative stress resulting in vascular MMP activation and corresponding functional and structural alterations in the vasculature, as compared with those found with the PPI omeprazole. Male Wistar rats were treated (4 weeks) with vehicle (2% tween 20), omeprazole (10 mg/Kg/day; i.p.) or ranitidine (100 mg/Kg/day; gavage). Then the aorta was collected to perform functional, biochemical, and morphometric analysis. Both ranitidine and omeprazole increased gastric pH and oxidative stress assessed in situ with the fluorescent dye dihydroethidium (DHE) and with lucigenin chemiluminescence assay. Both IGAS augmented vascular activated MMP-2. These findings were associated with aortic remodeling (increased media/lumen ratio and number of cells/μm2). Both IGAS also impaired the endothelium-dependent relaxation induced by acetylcholine (isolated aortic ring preparation). This study provides evidence that the H2RB ranitidine induces vascular dysfunction, redox alterations, and remodeling similar to those found with the PPI omeprazole. These findings strongly suggest that IGAS increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling, which helps to explain the increased cardiovascular risk associated with the use of those drugs.

Determination of omeprazole via fluorescence-quenching methodology; application to content uniformity testing.

A new, proven, economical spectrofluorimetric approach has been used to determine the proton pump inhibitor omeprazole (OMP). This innovative technique is based on the ability of OMP to quench the native fluorescence of the mercurochrome dye in an acidic (pH3.6) solution. Because it was discovered that quenching is proportional to the drug concentration, this dye was used as a sensor for OMP detection. The fluorescence intensity was measured at 518/540 nm, and its linear response ranged from 0.2-10.0μg/mL with a linear coefficient of 0.9999. The computation yielded a limit of quantification (LOQ) of 0.20 μg/mL and a limit of detection (LOD) of 0.07 μg/mL. Every circumstance and element impacting the reaction product was examined in detail. Pharmacopeial standards carried out the validation. The approved method investigated several commercial preparations and formulations, and the results were favorably compared with those provided by a reference method. According to United States Pharmacopeia (USP) rules, content consistency for two distinct formulations was evaluated.

Effects of treatment with clopidogrel with or without proton pump inhibitor omeprazole on the risk of ischemic stroke: a nationwide cohort study

Most proton pump inhibitors (PPIs) inhibit the bioactivation of clopidogrel to its active metabolite. There is controversy concerning whether PPIs alter the effectiveness of clopidogrel in reducing the risk of ischemic stroke (IS). We therefore aimed to examine the risk of IS associated with concomitant use of clopidogrel and omeprazole, a PPI commonly used in clinical settings. We conducted a retrospective cohort study using the National Health Insurance Research Database of Taiwan dated from 2000 to 2013. The study cohorts comprised 407 patients diagnosed with acute coronary syndrome (ACS) and with concomitant use of clopidogrel and omeprazole (the exposed cohort), 814 ACS patients with single use of clopidogrel (the comparison cohort), and 230 ACS patients with concurrent use of clopidogrel and pantoprazole (the reference cohort). The primary outcome was incident IS. The hazard ratios (HRs) and 95% confidence intervals (CIs) derived from the time-dependent Cox regression model were used to assess the association between concomitant use of clopidogrel and omeprazole and the risk of IS. The incidence rate of IS was significantly higher in the exposed cohort (81.67 per 1000 person-years) than in the comparison cohort (57.45 per 1000 person-years), resulting in an adjusted HR of 1.39 (95% CI 1.03–1.74). By contrast, there was no significant difference in the risk of IS between the exposed and reference cohorts (adjusted HR 1.11; 95% CI 0.81–1.52). The present study revealed that patients taking both clopidogrel and omeprazole was associated with an increased risk of IS.

Omeprazole induces profibrotic gene expression in rat kidney: implication of TGF-β/Smad signaling pathway

Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications. However, PPI usage is linked to a higher risk of both acute and chronic renal damage by mechanisms not entirely known. The present study demonstrates that omeprazole (10 mg/kg body weight, i.p.) causes TGF-β/Smad signaling activation and subsequent expression of the profibrotic genes CTGF and TIMP-1 in rat kidney. Increased production of CTGF and TIMP-1 accompany activation of the TGF-β/Smad signaling cascade. However, simultaneous treatment of omeprazole and the TGF-β inhibitor, disitertide (P144) (1 mg/kg body weight i.p.) suppresses the TGF-β/Smad signaling pathway and subsequent production of CTGF and TIMP-1. Additionally, TGF-β level in rat kidney was highly reduced in animals treated with the ROS (reactive oxygen species) scavenger, N-acetyl cysteine (NAC) (100 mg/kg body weight i.p.) before omeprazole administration. Furthermore, the reduction in SOD activity brought by omeprazole was returned to the normal level in those animals. However, MDA level increased by omeprazole was highly reduced in the presence of NAC. Collectively, the current findings demonstrate that omeprazole has the ability to promote the expression of the profibrotic genes CTGF and TIMP-1 in a ROS and TGF-β dependent manner. The present study suggests the co-use of ROS scavenger to improve the therapeutic use of the PPI omeprazole.

Study of the antiulcer activity of garden cabbage extract on the chronic acetic ulcer model in rats

The aim of the study was to study the gastroprotective properties of the dry extract of garden cabbage in the model of chronic acetic ulcer in rats.
 Materials and methods. Chronic ulcerative lesions of the gastric mucosa of rats were modeled by introducing 0.05 ml of a 30 % solution of acetic acid into the subserous layer of the stomach wall. The dry extract of garden cabbage in a conditionally therapeutic dose of 50 mg/kg and reference drugs omeprazole and altan were administered intragastrically for 10 days, starting from the second day of the experiment. When choosing the duration of the course of treatment, we proceeded from the data that the effectiveness of the antiulcer action in the clinic is assessed after 10-12 days of treatment. The percentage of animals with ulcers in the group, the state of the gastric mucosa were evaluated, the ulcer index and antiulcer activity were calculated. To elucidate the possible mechanism of action of the extract, we studied its effect on synthetic processes in terms of the content of RNA and DNA in homogenates of the gastric mucosa by the spectrophotometric method by reaction with perchloric acid.
 Results. On the model of stomach damage, caused by acetic acid, a pronounced antiulcer activity of the extract (54.26) was established at the level of omeprazole (54.62). The maximum antiulcer activity (72.75) was revealed when using the combination of the extract with omeprazole, which, in terms of ulcerative effect, is superior to monotherapy with the extract, omeprazole and altan (35.08).
 Reparative regeneration is a component of an adaptive tissue reaction; under conditions of violation of the reparative potencies of the mucosa, chronic diseases of the gastrointestinal tract develop. Since the final goal of antiulcer therapy is the healing of the ulcer, and the basis of this process is reparative regeneration, the reparative properties of the extract have been studied. Under the influence of cabbage extract, the content of RNA and DNA in the mucosa probably increased by 2.8 and 2.4 times, respectively, at the same level with omeprazole. If possible, to activate the synthetic processes of DEGC and omeprazole, altan significantly prevailed.
 The most pronounced effect of enhancing reparative processes was established with the combined use of the extract and omeprazole, which turned out to be a significant increase in the content of RNA and DNA in the gastric mucosa by 3.2 and 2.9 times compared with the control.
 Conclusions. On the model of chronic damage to the stomach of rats, cabbage extract showed an antiulcer effect, the severity of which was not inferior to the comparison drug, the proton pump inhibitor omeprazole, and significantly exceeded the phytopreparation - altan. The combined use of the extract and omeprazole showed the highest preventive effect of preventing the negative effects of acetic acid on the gastric mucosa. One of the mechanisms of the gastroprotective action of the extract is its ability to enhance reparative processes in the gastric mucosa. The results obtained indicate the prospects for further research on the antiulcer properties of cabbage extract with a view to its use in the complex therapy of peptic ulcer

Therapeutic efficacy of proton pump inhibitor (omeprazole) on cryptosporidiosis parvum in immunosuppressed experimental mice.

Cryptosporidiosis is one of the most frequent food and water-borne diseases. The disease might be life-threatening in immunosuppressed patients. Unfortunately, the only approved drug, nitazoxanide, is with variable efficacies, particularly in malnourished children and immunocompromised patients. Therefore, there is a need to discover an alternative treatment that could be achieved by targeting the metabolic pathways. One of the important enzymes in the glycolysis pathway of C. parvum is triosephosphate isomerase, which could be hindered by the proton pump inhibitor (PPI) omeprazole. In this study, omeprazole was repurposed against C. parvum infection in experimentally immunosuppressed mice. This study was conducted on five mice groups (n = 10). Group I (Normal Control), group II (Infected Control): Mice were infected orally with 1 × 105 C. parvum oocysts on the 15th day of DEX induced immunosuppression. Group III (NTZ-treated): infected and treated by NTZ. Group IV (Omeprazole-treated), and lastly, Group V (NTZ + Omeprazole-treated). The result obtained with omeprazole alone was better than nitazoxanide regarding oocyst shedding reduction percentages (84.9% & 56.1%, respectively). Also, it was better regarding restoration of histopathological and ultrastructural architectures, improvement of liver enzymes (alanine aminotransferase and aspartate aminotransferase) and renal functions (urea and creatinine), and the reduction of C. parvum triosephosphate isomerase (TIM) gene expression by RT-PCR. However, the best results were obtained with the combined treatment. Hence, omeprazole could be considered a novel drug option to treat this life-threatening parasitic infection either alone or combined with NTZ, especially in immunosuppressed patients.

Abstract CT264: Taking sotorasib with an acidic beverage improves sotorasib exposure for subjects on omeprazole

Abstract The solubility of KRASG12C inhibitor sotorasib is pH dependent and coadministration with a proton pump inhibitor (omeprazole) decreased sotorasib maximum concentration (Cmax) by 56.9% and the area under the concentration curve from time zero to the time of the last quantifiable concentration (AUClast) by 42.4% under fasted conditions. This study in healthy volunteers evaluated if taking sotorasib with an acidic beverage such as Coca Cola would alter sotorasib absorption when coadministered with omeprazole and improve sotorasib exposure. Two separate phase 1, open-label, fixed sequence, 2-period studies enrolled at least 14 healthy subjects each. In the first study, each subject received a single 960 mg dose of sotorasib under fasted conditions on day 1, followed by omeprazole 40 mg once daily for 5 days on days 4 to 8, and then received omeprazole 40 mg in combination with sotorasib 960 mg on day 9 with water. For the second phase 1 study all conditions were kept the same except subjects received omeprazole in combination with sotorasib on day 9 with an 8-ounce (240 mL) glass of acidic beverage (Coca-Cola) instead of water. In both studies, intensive pharmacokinetic plasma sampling occurred predose and at 13 timepoints up to 48 hours post-dose. Sotorasib plasma concentrations were measured using a validated high-performance liquid chromatography tandem mass spectrometry method. Non-compartmental analysis was used to calculate pharmacokinetic parameters. Safety and tolerability were monitored throughout the study. Increased sotorasib exposure was observed when sotorasib and omeprazole were taken with an acidic beverage compared to when sotorasib and omeprazole were taken with water for both AUClast (23200 vs 16700 h∙ng/mL respectively) and Cmax (4850 ng/mL vs 3110 ng/mL respectively). Compared to the geometric mean ratio of sotorasib and omeprazole taken with water, taking sotorasib and omeprazole with an acidic beverage resulted in an increase of 19.0 percentage-point in AUClast and a 24.6 percentage-point increase in Cmax. Coadministration of sotorasib and omeprazole with Coca Cola was safe and well tolerated. For patients on acid-reducing drugs, sotorasib taken with an acidic beverage is an effective strategy to increase sotorasib exposure and counteract the reduced exposures resulting from the drug-drug interaction effect of acid-reducing drugs. Citation Format: Natasha Strydom, Panli Cardona, Marintan Spring, Jessica Purkis, Brett Houk. Taking sotorasib with an acidic beverage improves sotorasib exposure for subjects on omeprazole [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT264.

Prevalence and Safety of Prescribing PPIs with Clopidogrel in Palestine.

Proton pump inhibitors (PPIs) are commonly prescribed medications that are thought to increase the risk of cardiovascular events because they reduce the effectiveness of clopidogrel via shared hepatic pathways. This study examined the prevalence of concomitant prescribing of clopidogrel/PPI among patients diagnosed with acute coronary syndrome and the adverse cardiovascular event associated with this interaction. A retrospective cohort study was conducted by retrieving patient data from the Nat Health Insurance claims processor database in Palestine. Adults diagnosed with Acute Coronary Syndrome (ACS) from 2019 through 2021 who were prescribed clopidogrel or clopidogrel in combination with a PPI were included in the study. Endpoints were adverse cardiac events, including readmission for revascularization during the first year of treatment. The study included 443 patients; the prevalence of prescribing concomitant clopidogrel with a PPI was 74.7%, whereas 49.2% were prescribed interacting PPI (omeprazole, esomeprazole, and lansoprazole). 59 (13.3%) of participants experienced a cardiovascular event within 1 year of starting therapy, including 27 (12.4%) patients who had a cardiovascular event while taking an interacting PPI. No significant association was found between PPI administration and increased CV event risk in patients receiving concomitant clopidogrel and PPIs therapy (p = 0.579). In this study, we observed a high prevalence of prescribing a PPI in combination with clopidogrel, regardless of the FDA recommendations. No significant increase in cardiovascular events was observed in patients receiving concomitant clopidogrel and PPI therapy.

Proton pump inhibitor-induced risk of chronic kidney disease is associated with increase of indoxyl sulfate synthesis via inhibition of CYP2E1 protein degradation

Proton pump inhibitors (PPIs) are widely used to treat acid-related disorders in the gastrointestinal tract; however, PPI use increases the risk of chronic kidney disease (CKD) through unclear mechanisms. Considering that PPIs disturb the gut microbiome balance, which is involved in the precursor of gut-derived uremic toxin accumulation, and that gut-derived uremic toxins aggravate CKD progression, the aim of this study is to elucidate whether PPIs affect gut-derived uremic toxin metabolism, including indoxyl sulfate (IS), p-cresyl sulfate, and trimethylamine-N-oxide, as a mechanism for causing CKD. The present study showed that 3 week-treatment of PPIs (omeprazole, lansoprazole, and pantoprazole at 30 mg/kg) in mice only increased IS plasma levels among the above three gut-derived uremic toxins. Additionally, lansoprazole increased IS plasma concentrations along with increased exposure dose (7.5–30 mg/kg) and duration (1–3 weeks). However, nephrotoxicity with mild changes in glomerular structure and signs of fibrosis were observed only in groups exposed to a 3-week treatment of PPIs (30 mg/kg). As the concentrations of indole (the precursor of IS from gut metabolism) in the colon were only increased in the pantoprazole-treated group, the mechanism of increased IS exposure remains unclear. Further studies revealed that PPIs (omeprazole and lansoprazole; but not pantoprazole) increased IS production from indole in primary mouse hepatocytes in a concentration-dependent manner. Additionally, the increased protein levels of hepatic CYP2E1 (the key enzyme mediating IS formation) due to suppressed degradation resulted in an increase in IS levels. Although omeprazole and lansoprazole significantly inhibited IS uptake in hOAT1/3 in vitro, 3 weeks of PPI treatment did not reduce IS renal excretion in mice. In conclusion, PPIs induced IS synthesis via increased hepatic CYP2E1 protein level, subsequently leading to increased IS exposure. These findings present a plausible biological mechanism to explain the association of PPI use with the increased risk of CKD.

Clinician adherence to pharmacogenomics prescribing recommendations in clinical decision support alerts.

Thoughtful integration of interruptive clinical decision support (CDS) alerts within the electronic health record is essential to guide clinicians on the application of pharmacogenomic results at point of care. St. Jude Children's Research Hospital implemented a preemptive pharmacogenomic testing program in 2011 in a multidisciplinary effort involving extensive education to clinicians about pharmacogenomic implications. We conducted a retrospective analysis of clinicians' adherence to 4783 pharmacogenomically guided CDS alerts that triggered for 12 genes and 60 drugs. Clinicians adhered to the therapeutic recommendations provided in 4392 alerts (92%). In our population of pediatric patients with catastrophic illnesses, the most frequently presented gene/drug CDS alerts were TPMT/NUDT15 and thiopurines (n = 3850), CYP2D6 and ondansetron (n = 667), CYP2D6 and oxycodone (n = 99), G6PD and G6PD high-risk medications (n = 51), and CYP2C19 and proton pump inhibitors (omeprazole and pantoprazole; n = 50). The high adherence rate was facilitated by our team approach to prescribing and our collaborative CDS design and delivery.

Assessing the Potential of Untargeted SWATH Mass Spectrometry-Based Metabolomics to Differentiate Closely Related Exposures in Observational Studies.

Mass spectrometry (MS) is increasingly used in clinical studies to obtain molecular evidence of chemical exposures, such as tobacco smoke, alcohol, and drugs. This evidence can help verify clinical data retrieved through anamnesis or questionnaires and may provide insights into unreported exposures, for example those classified as the same despite small but possibly relevant chemical differences or due to contaminants in reported exposure compounds. Here, we aimed to explore the potential of untargeted SWATH metabolomics to differentiate such closely related exposures. This data-independent acquisition MS-based profiling technique was applied to urine samples of 316 liver and 570 kidney transplant recipients from the TransplantLines Biobank and Cohort Study (NCT03272841), where we focused on the immunosuppressive drug mycophenolate, which is either supplied as a morpholino-ester prodrug or as an enteric-coated product, the illicit drug cocaine, which is usually supplied as an adulterated product, and the proton pump inhibitors omeprazole and esomeprazole. Based on these examples, we found that untargeted SWATH metabolomics has considerable potential to identify different (unreported) exposure or co-exposure metabolites and may determine variations in their abundances. We also found that these signals alone may sometimes be unable to distinguish closely related exposures, and enhancement of differentiation, for example by integration with pharmacogenomics data, is needed.

Helicobacter Pylori, Infection, Virulence Factors and Treatment A Review

Gastric and ulcer peptic disease is a common disease in the community. Considering the close relationship between peptic ulcer and gastritis caused by Helicobacter pylori. The prevalence of H. pylori increased markedly with age with the maximum colonization (81.5%) occurring in adults (40-60 years). H. pylori are bacteria that can cause an infection in the stomach or duodenum (first part of the small intestine). It’s the most common cause of peptic ulcer disease. H. pylori can also inflame and irritate the stomach lining (gastritis). Untreated, long-term H. pylori infection can lead to stomach cancer (rarely). H. pylori multiply in the mucus layer of the stomach lining and duodenum. The bacteria secrete an enzyme called urease that converts urea to ammonia. This ammonia protects the bacteria from stomach acid. As H. pylori multiply, it eats into stomach tissue, which leads to gastritis and/or gastric ulcer. Symptoms include dull or burning stomach pain, unplanned weight loss and bloody vomit. H-pylori-caused ulcers are commonly treated with combinations of antibiotics. Usually two antibiotics are prescribed. Among the common choices are amoxicillin, clarithromycin (Biaxin®), metronidazole (Flagyl®) and tetracycline and Proton pump inhibitor: Commonly used proton pump inhibitors include lansoprazole (Prevacid®), omeprazole (Prilosec®), pantoprazole (Protonix®), rabeprazole (Aciphex®) or esomeprazole (Nexium®). and Bismuth subsalicylate: Sometimes this drug (eg, Pepto-Bismol®) is added to the antibiotics plus proton pump inhibitor combinations mentioned above. This drug protects the stomach lining. combination treatment is usually taken for 14 days. One newer medication, Talicia®, combines two antibiotics (rifabutin and amoxicillin) with a proton pump inhibitor (omeprazole) into a single capsule.

Impact of Helicobacter pylori Infection and Outcome of Anti-Helicobacter pylori Therapy in Patients with Reflux Laryngopharyngitis.

Objectives This study was designed to explore the relationship between Helicobacter pylori (Hp) infection and reflux laryngopharyngitis (RLP) and to evaluate the outcome of anti-Hp therapy in improving RLP symptoms. Methods A total of 410 patients with RLP were enrolled and tested for Hp infection. The association of Hp infection with reflux symptom index (RSI) and reflux finding score (RFS) was determined. Hp-positive patients received either a proton pump inhibitor (PPI) omeprazole alone (control group) or a combination regimen (experimental group) consisting of omeprazole, mosapride citrate, amoxicillin, and clarithromycin. Therapeutic outcomes were compared 4 weeks later. Results Of the 410 participants, 290 were Hp-positive and 120 Hp-negative. Both RSI and RFS were significantly higher in Hp-positive patients than in Hp-negative patients. Hp infection status was positively correlated with RSI (P < 0.05) and RFS (P < 0.05). The overall response rate was higher in the experimental group than in the control group. Both the groups had a significant reduction in RSI and RFS after therapy, with a greater improvement in the experimental group (P < 0.05). Conclusion Our findings establish a link between Hp infection and RLP. Anti-Hp therapy improves RSI and RFS in RLP patients. Therefore, Hp eradication drugs may be added to the PPI-based regimen in the treatment of RLP.

A systematic review on diverse synthetic route and pharmacological activities of benzimidazole as optimized lead

The aim of this review is to provide the systematic information of synthetic scheme and biological activity of synthesized benzimidazole derivatives. Benzimidazole is widely used lead molecule for the synthesis of various types of pharmacologically active moiety. It is heterocyclic aromatic fused colorless solid having molecular mass of 118.053 g/mol. It is basic in nature and can be served as ligand in coordination chemistry. It is bioactive compound showed various pharmacological activity till now viz. anthelmintics (albendazole, mebendazole), proton pump inhibitors (omeprazole, pantoprazole), antibiotics, antiprotozoal, antifungal, anticancer, anti-viral, anti-oxidant, anti-inflammatory etc. Various synthetic route by various methods is also already reported. Some of them are traditional convenient method, microwave reactor method, solvent free synthesis method, green synthesis method. Due to its wide variety of biological action and the similarity with biomolecule, it is frequently taken as lead for new drug discovery

Trends in proton pump inhibitor use, reflux esophagitis, and various upper gastrointestinal symptoms from 2010 to 2019 in Japan.

The increasing usage of proton pump inhibitors (PPIs) has been reported worldwide, but information on PPI use in East Asia is inadequate. This study aimed to examine the trends in PPI use in Japan, along with the changes in histamine H2 receptor antagonist (H2RA) use, disease rate of reflux esophagitis, and the prevalence of upper gastrointestinal symptoms. We analyzed 217,712 healthy subjects (127,607 men and 90,105 women; 51.4 ± 9.7 years old) participating in the health check program from 2010 to 2019. Various upper gastrointestinal symptoms were evaluated using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire. Reflux esophagitis was diagnosed by esophageal erosion using the Los Angeles classification grades A, B, C, and D. From 2010 to 2019, the percentage of PPI users increased markedly from approximately 1.8% to 5.3%, whereas that of H2RA users decreased gradually from approximately 2.5% to 1.9%. The use of all classical types of PPIs (omeprazole, lansoprazole, rabeprazole, and esomerazole) and a new type of PPI, a potassium-competitive acid blocker (vonoprazan), greatly increased during the 10 years. An upward trend in the prevalence of reflux esophagitis was observed from 2010 to 2015, but not from 2016 to 2019, indicating that the monotonic rising prevalence of reflux disease stopped in the middle of the 2010s in Japan. In contrast, various upper gastrointestinal symptoms significantly improved between 2010 and 2019. All 12 FSSG symptoms of PPI users were significantly worse than those of non-PPI users, suggesting that PPIs still cannot completely control upper gastrointestinal symptoms. In conclusion, this study revealed a significant increase in PPI use and a slight decrease in H2RA use from 2010 to 2019. Despite a plateau in the prevalence of reflux esophagitis and considerable improvement in various upper gastrointestinal symptoms, PPI use has continued to increase in Japan.

Results From Phase I Studies Investigating the Dose Linearity of Finerenone Tablets and the Influence of Food or pH-Modifying Comedications on its Pharmacokinetics in Healthy Male Volunteers

Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that reduces the risk of adverse kidney and cardiovascular outcomes in patients with chronic kidney disease associated with type 2 diabetesmellitus. Clinical phase I studies with finerenone were carried out to assess its pharmacokinetics and the influence of common covariables on its absorption after oral administration. Three crossover studies in healthy male volunteers with single-dose administration of finerenone investigated the dose linearity of a film-coated tablet (1.25-10 mg [n = 24] and 10-20 mg [n = 18]), the effect of food on the 20 mg tablet (n = 18), and the effects of the proton-pump inhibitor omeprazole (4 days pre-treatment and co-administration 2 h before finerenone) and an aluminum/magnesium hydroxide-containing antacid (10 mL [Maalox®] 70 mVal, simultaneous intake) on the 10mg tablet (n = 10 and n = 11, respectively). Finerenone was rapidly absorbed (time to reach maximum plasma concentration [tmax] was 0.50-0.75 h). Area under the curve from zero to infinity (AUC∞) and the maximum concentration (Cmax) increased in proportion to dose in the range investigated in clinical phase II and phase III studies (1.25-20mg), with point estimates for the ratio of dose-normalized AUC∞ and Cmax (20 mg/10 mg, approved therapeutic doses) of 0.9943 and 0.9301. After the administration of finerenone 20mg with a high-fat, high-calorie meal, AUC∞ increased (+21%), Cmax decreased (-19%), and tmax was prolonged (2.47vs. 0.75 h) when compared with the fasting state. Omeprazole had no effect on finerenone AUC∞ and Cmax. Maalox had no effect on finerenone AUC∞ and led to a non-clinically-relevant decrease in Cmax (-19%). The pharmacokinetics of the finerenone film-coated tablet were linear. High-fat, high-calorie food had no clinically relevant effect on the pharmacokinetics of finerenone. In addition, pH-modifying comedications were not found to alter the pharmacokinetics of finerenone and were deemed safe for co-administration.