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Background: Due to general unavailability and common side effects of tetracycline, the clinical application of bismuth quadruple therapy (BQT) is greatly limited. Whether amoxicillin can replace tetracycline in BQT remains unknown. This study aimed to compare the eradication rate, safety and compliance between amoxicillin‐containing and tetracycline‐containing BQT as a first‐line regimen for Helicobacter pylori eradication. Methods: This randomized trial was conducted on 404 naïve patients for H. pylori eradication. The participants were randomly assigned to 14‐day amoxicillin‐containing (bismuth potassium citrate 110 mg four times/day, esomeprazole 20 mg twice daily, metronidazole 400 mg four times/day and amoxicillin 500 mg four times/day) and tetracycline‐containing (tetracycline 500 mg four times/day and the other three drugs used as above) BQT. Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed 4–8 weeks after eradication to evaluate outcome. Results: As for the eradication rates of amoxicillin‐containing and tetracycline‐containing BQT, the results of both intention‐to‐treat and per‐protocol analyses showed that the difference rate of the lower limit of 95% confidence interval was above −10.0% (intention‐to‐treat analysis: 81.7% vs. 83.2%, with a rate difference of −1.5% [−6.3% to 9.3%]; per‐protocol analysis: 89.0% vs. 91.6%, −2.6% [−4.1% to 9.3%]). The incidence of adverse events in amoxicillin‐containing BQT was significantly lower than tetracycline‐containing BQT (29.5% vs. 39.7%). Both groups achieved relatively good compliance (92.0% vs. 89.9%). Conclusion: The eradication efficacy of amoxicillin‐containing BQT was non‐inferior to tetracycline‐containing BQT as a first‐line regimen for H. pylori eradication with better safety and similar compliance. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate and to compare the clinical, hemato-biochemical and endoscopic aspects of gastropathy in dogs treated with meloxicam alone or incombination with esomeprazole and misoprostol. Twenty baladi healthy dogs were included in the experimental study. Dogs were divided into four groups each group consisting of five animals; Group I (control group), the group that does not receive any medication. Meloxicam treated groups divided into: Group II which received meloxicam at a dose of 0.2 mg/kg BWT per OS /24 hr. Group III animals received the same previous dose of meloxicam and esomeprazole at a dose of 1mg/kg BWT per OS /24 hr. Group IV animals received the same dose of meloxicam and misoprostol 3μg /kg BWT per OS tid. Upon drug administration, dogs were kept under observation for 14 consecutive days. Clinical and hemato-biochemical analysis were evaluated across time (T0, T3, T7, T10 and T14). The image analysis of the gastroscopic examination was evaluated across time (T0, T7 and T14), endoscopic examinations were applied to all animals in four groups at three time points (T0, T7, and T14), endoscopic lesions were scored by use of a 5-point scale. Clinically, the most common clinical sings in dogs with Meloxicam induced- gastropathy were inappetence to anorexia, hematemesis, melena, abdominal pain and weakness, the specific endoscopic lesions of gastropathy were gastric erosion, hemorrhage and ulcers. Serum gastrin concentration is a biochemically sensitive indicator of gastropathy. The overall results concluded that meloxicam-induced gastropathy was more severe in group II compared to groups III and group IV. The proton pump inhibitor (esomeprazole) was more effective and better tolerated than misoprostol. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to explore the time-course of hospitalization due to hyponatremia associated with omeprazole and esomeprazole. Methods: In this register-based case–control study, we compared patients hospitalized with a main diagnosis of hyponatremia (n = 11,213) to matched controls (n = 44,801). We used multiple regression to investigate time-related associations between omeprazole and esomeprazole and hospitalization because of hyponatremia. Results: The overall adjusted OR (aOR) between proton pump inhibitor (PPI) exposure, regardless of treatment duration and hospitalization with a main diagnosis of hyponatremia, was 1.23 (95% confidence interval CI 1.15–1.32). Exposure to PPIs was associated with a prompt increase in risk of hospitalization for hyponatremia from the first week (aOR 6.87; 95% CI 4.83–9.86). The risk then gradually declined, reaching an aOR of 1.64 (0.96–2.75) the fifth week. The aOR of ongoing PPI treatment was 1.10 (1.03–1.18). Conclusion: The present study shows a marked association between omeprazole and esomeprazole and hyponatremia related to recently initiated treatment. Consequently, newly initiated PPIs should be considered a potential culprit in any patient suffering from hyponatremia. However, if the patient has had this treatment for a longer time, the PPI should be considered a less likely cause. [ABSTRACT FROM AUTHOR]

Background/Aims Patients with gastroesophageal reflux disease (GERD) frequently experience nighttime heartburn and sleep disturbance. Tegoprazan is a new potassium-competitive acid blocker that can rapidly block acid secretion. This study aims to evaluate the efficacy of tegoprazan compared with esomeprazole in relieving nighttime heartburn and sleep disturbances. Methods Patients with erosive esophagitis, nighttime heartburn, and sleep disturbances were randomized to receive tegoprazan 50 mg or esomeprazole 40 mg for 2 weeks. The primary endpoint was time to first nighttime heartburn-free interval. The percentage of nighttime heartburn-free days was also compared between the 2 groups. Results A total of 46 patients were enrolled in this study. Time to the first nighttime heartburn-free interval was shorter with tegoprazan than with esomeprazole but the difference was not statistically significant (1.5 days vs 3 days, P = 0.151). The percentage of nighttime heartburn-free days was higher in the tegoprazan group but the difference was insignificant (57.8% vs 43.1%, P = 0.107). Adverse events occurred in 2 patients. They were mild in severity. Conclusions Tegoprazan may induce faster relief of nighttime heartburn symptoms and may improve sleep disorders associated with nighttime heartburn. Further large-scale studies are required to validate our findings. [ABSTRACT FROM AUTHOR]

Background: Proton‐pump inhibitors (PPIs) are cornerstone treatments for gastro‐esophageal reflux disease (GERD); however, evidence suggests that most patients exhibit partial response to PPIs, suggesting the need for novel therapies that can provide an improved and sustained increase in gastric pH. Aims: This study aimed to determine the effect of vonoprazan, a novel, orally active small‐molecule potassium‐competitive acid blocker, versus esomeprazole, a PPI, in preventing heartburn symptoms over a 4‐week treatment period in patients with GERD and a partial response to esomeprazole treatment. Methods: This randomized, double‐blind, proof‐of‐concept, phase 2 clinical trial was conducted between 2016 and 2018 at 39 sites across Europe and designed to evaluate the efficacy and safety of vonoprazan 20 mg once daily (q.d.) and 40 mg q.d. versus esomeprazole 40 mg q.d. after 1:1:1 randomization of symptomatic patients with GERD and a partial response to a healing dose of esomeprazole. Results: Overall, 256 eligible patients (female, 59.4%; mean age, 52.6 years) received vonoprazan 20 mg (n = 85), vonoprazan 40 mg (n = 85), or esomeprazole 40 mg (n = 86); mean (SD) percentages of heartburn‐free 24‐h periods during double‐blind treatment were 36.7% (33.4%), 36.5% (35.6%), and 38.4% (34.8%), respectively, with no intergroup statistical significance. Vonoprazan exposure increased proportionally from the 20‐mg to 40‐mg dose (mean Cmax: 23.3 ng/ml to 47.1 ng/ml, respectively). Most treatment‐emergent adverse events were mild, with no deaths reported. Conclusions: No statistically significant difference in efficacy and safety was observed among treatment groups, and vonoprazan was well tolerated. The trial is registered with the National Board of Health (EudraCT: 2015–001154‐14) database. [ABSTRACT FROM AUTHOR]

Background: Posaconazole is widely used for the prophylaxis and treatment of invasive fungal diseases. Because of the limited and variable absorption of the initially available oral suspension, a delayed-release tablet and intravenous formulation were developed. Objective: This study aimed to characterize the pharmacokinetics, including the absolute oral bioavailability, of all posaconazole formulations in healthy volunteers. Methods: Data from 182 healthy volunteers with 3898 densely sampled posaconazole concentrations were pooled from eight phase I clinical studies on the three formulations of various single and multiple dosage regimens between 50 and 400 mg. Analysis and simulations were performed using NONMEM 7.5.0. In the covariate analysis, the influence of food (fed vs fasted), nonlinearity, and for the delayed-release tablet, comedication (antacid, ranitidine, esomeprazole, and metoclopramide) were tested. Results: A two-compartment model with respectively, four and eight absorption transit compartments, best described the profiles of the oral suspension and delayed-release tablet. For the suspension, both a food effect and a dose-dependent nonlinear bioavailability were quantified, resulting in lower bioavailability when fasted or at a higher dose. The typical bioavailability of the suspension at 100 mg and 400 mg was derived to be respectively, 17.1% and 10.1% under fasted conditions and 59.1% and 49.2% under fed conditions. The absolute bioavailability of the delayed-release tablet was 58.8% (95% confidence interval 33.2–80.4) under fasted conditions and approached complete absorption under fed conditions for dosages up to 300 mg. Food intake reduced the absorption rate constant of the suspension by 52.2% (confidence interval 45.2–59.2). The impact of comedication on the absorption of the delayed-release tablet was not statistically significant. Model-based simulations indicate that under fed conditions, the licensed dosages of the three formulations yield a steady-state trough concentration ≥ 0.7 mg/L in over 90% of healthy volunteers. About 35% of healthy volunteers who receive the licensed 300-mg delayed-release tablet under fasted conditions do not achieve this target, while for the suspension this percentage varies between 55 and 85%, depending on the dose. Conclusions: For both oral posaconazole formulations, we quantified bioavailability and absorption rate, including food effects, in healthy volunteers. The pharmacokinetic superiority of the delayed-release tablet was demonstrated under both fed and fasted conditions, compared with the oral suspension. The impact of food on the bioavailability of the delayed-release tablet was larger than anticipated, suggesting that administering the delayed-release tablet with food enhances absorption. [ABSTRACT FROM AUTHOR]

Background: Aging may affect the efficacy of Helicobacter pylori eradication. The aim of our study was to assess the efficacy and safety of 7-day non-bismuth concomitant quadruple therapy as a first-line H. pylori infection eradication regimen in elderly individuals. Methods: We retrospectively analyzed a cohort with prospectively collected data from January 2013 to December 2019 at Chang Gung Memorial Hospital in Kaohsiung. There were 408 naive infected subjects aged 20 years or older who were treated with 7 days of concomitant therapy as a first-line H. pylori eradication regimen. We divided the patients into an elderly group (aged ≥ 65 years) and a control group (aged < 65 years). Two patients were lost during follow-up in the elderly group and 29 patients were lost in the control group, resulting in 56 in the ≥ 65-year age group and 321 in the control group. The patients were asked to perform urea breath tests 8 weeks later. Results: The eradication rates for the elderly and control groups were 93.1% (95% confidence interval (CI): 83.3–98.1) and 84.0% (95% CI 79.7–87.7) (p = 0.070), respectively, in the intention-to-treat analysis, and 96.4% (95% CI 87.6–99.6) and 91.6% (95% CI 88.0–94.4) (p = 0.210), respectively, in the per-protocol (PP) analysis. The adverse event rates were 8.9% in the elderly group and 12.8% in the control group (p = 0.417). The compliance was 100% in both groups. No significant difference was seen in antibiotic resistance in either group. Multivariate analysis revealed that metronidazole resistance (odds ratio (OR) 6.870, 95% CI 1.182–39.919, p = 0.032) and dual-therapy resistance (OR 7.188, 95% CI 1.326–38.952, p = 0.022) were independent factors for eradication failure. Conclusions: The efficacy of non-bismuth concomitant quadruple therapy in the elderly cohort was comparable with that in the non-elderly cohort for first-line H. pylori eradication with acceptable adverse effects. [ABSTRACT FROM AUTHOR]

A 72-year-old patient presented with malaena secondary to two antral ulcers which were discovered in oesophagogastroduodenoscopy (OGD) after admission. One of the ulcers with a visible vessel was injected with adrenaline and clipped with an OVESCO clip. The patient continued to have coffee ground vomitus on the following day with a drop in haemoglobin level. Repeat OGD showed a large intra-mural haematoma with the clip still in situ and no bleeding from the surface of the ulcer. Patient underwent a coil embolization of the distal gastroduodenal artery (GDA), right gastroepiploic artery and a medial branch of the GDA. Repeat OGD showed that the submucosal haematoma had evacuated, leaving a large, cleanbased mucosal defect. [ABSTRACT FROM AUTHOR]

Summary: In this case report, we present a rare case of life‐threatening gastrointestinal haemorrhage associated with deranged coagulation due to supratherapeutic levels of dabigatran. Dabigatran is a potent, synthetic, reversible non‐peptide thrombin inhibitor which is increasingly used for stroke prevention in patients with non‐valvular atrial fibrillation. It is generally accepted that dabigatran dosing does not require titration or the monitoring of plasma levels due to its predictable pharmacokinetics and pharmacodynamics. However, this case report challenges this viewpoint while identifying an important knowledge gap in relation to the effect of altered gastrointestinal motility on the absorption of direct oral anticoagulants. Furthermore, it demonstrates the successful use of high‐dose idarucizumab in a critical care setting. Idarucizumab is a monoclonal antibody fragment that binds specifically to dabigatran and its metabolites, thereby reversing the anticoagulant effect. [ABSTRACT FROM AUTHOR]

Naproxen is a Nonsteroidal Anti-Inflammatory Drug (NSAID). It is mostly used to treat pain or inflammation caused by conditions such as arthritis, gout, tendinitis or menstrual cramps. Naproxen is available in isolated dose with various similar anti-inflammatory drugs, i.e.; esomeprazole, pantoprazole, paracetamol, ranitidine, sumatriptan and ibuprofen. This survey evaluates various methods for the analysis of Naproxen in bulk drugs and formulated products. Analytical procedures are critical for determining compositions, they allow as to obtain both qualitative and quantitative results utilizing by the advanced analytical tools. This include HPLC, HPTLC, UV- spectrophotometry, capillary electrophoresis, and electrochemical methods. The UV-spectrophotometry method is applied for the investigation of Naproxen in biological media, bulk samples and in various dosage formulations. The HPLC technique of Naproxen alone and the combination, including parameters such as matrix, stationary phase, mobile phase, wavelength detection, etc. HPTLC method parameters such as stationary phase, mobile combination phase, RF value, etc. To maintain high commercial product quality standards and to adhere to regulatory requirements, analytical technique development is necessary. Drug concentrations are measured using bioanalytical techniques. Development and validation of bioanalytical method is important to understand the pharmacokinetics of any drug and/or its metabolites. [ABSTRACT FROM AUTHOR]

Abstract Background Proton-pump inhibitors (PPI) are liberally prescribed in patients with liver cirrhosis. Observational studies link PPI therapy in cirrhotic patients with an increased risk for infectious complications, hepatic encephalopathy and an increased risk for hospitalization and mortality. However, patients with liver cirrhosis are also considered to be at risk for peptic ulcer bleeding. The STOPPIT trial evaluates if discontinuation of a pre-existing PPI treatment delays a composite endpoint of re-hospitalization and/or death in patients (recently) hospitalized with liver cirrhosis compared to patients on continued PPI medication. Methods The STOPPIT-trial is a prospective, multicentre, randomized, double-blinded, placebo-controlled, parallel-group trial. In total, 476 patients with complicated liver cirrhosis who already receive long-term PPI therapy without evidence-based indication are 1:1 randomized to receive either esomeprazole 20 mg (control group) or placebo (intervention group) for 360 days. Patients with an indication for PPI therapy (such as a recent diagnosis of peptic ulcers, severe reflux esophagitis, severe hemorrhagic gastritis, recent endoscopic therapy for oesophageal varices) are excluded. The primary composite endpoint is the time-to re-hospitalization and/or death. Secondary endpoints include rates of re-hospitalization, mortality, occurrence of infections, hepatic decompensation and acute-on-chronic liver failure. The safety endpoint is defined as manifestation of an evidence-based indication for PPI re-therapy. The impact of PPI continuation or discontinuation on the intestinal microbiota will be studied. The recruitment will take place at 18 study sites throughout Germany. Recruitment has started in April 2021. Discussion The STOPPIT trial is the first clinical trial to study the effects of PPI withdrawal on relevant outcome variables in patients with complicated liver cirrhosis. If the hypothesis that PPI withdrawal improves clinical outcomes of cirrhosis patients is confirmed, this would argue for a strong restriction of the currently liberal prescription practice of PPIs in this population. If, on the other hand, the trial demonstrates an increased risk of gastrointestinal bleeding events in patients after PPI withdrawal, this could create a rationale for a more liberal, prophylactic PPI treatment in patients with liver cirrhosis. Trial registration EU clinical trials register EudraCT 2019-005008-16 (registered December 27, 2019). ClinicalTrials.gov NCT04448028 (registered June 25, 2020). German Clinical Trials Register DRKS00021290 (registered March 10, 2021).

The Journal of Clinical Medicine retracted an article comparing Fexuprazan and Esomeprazole for treating erosive esophagitis due to concerns about data overlap with a previous publication by a different authorship group. Following an investigation confirming significant similarity between the two publications, the Editorial Board deemed the article redundant and retracted it in accordance with MDPI's policy. The retraction was approved by the Editor-in-Chief, and the authors agreed to it. [Extracted from the article]

• This was a randomised, positive drug-controlled study with a non-inferior design. • This study evaluated the efficacy of keverprazan-based quadruple therapy for Helicobacter pylori infection. • A regimen of keverprazan 20 mg twice daily proved to be effective against H. pylori. • The eradication rate with keverprazan therapy was superior to that with proton pump inhibitor (PPI) in the per protocol set. Keverprazan is a novel potassium-competitive acid blocker. The advantages of keverprazan as a potent acid suppressor in Helicobacter pylori eradication have not yet been demonstrated. The aim of this study was to evaluate the efficacy of keverprazan as a component of bismuth quadruple therapy in H. pylori treatment. Adult patients with H. pylori infection were enrolled and randomised to take keverprazan (KEV group)- or esomeprazole (ESO group)-quadruple therapy. The regimens contained keverprazan 20 mg or esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 240 mg and were administered twice daily for 14 days. The primary endpoint was the H. pylori eradication rate at 4 weeks after treatment. The full analysis set showed that the H. pylori eradication rates were 87.8% (252/287) and 82.52% (236/286) for the KEV and ESO groups, respectively (difference: 5.29%; 95% confidence interval [CI]: -0.55–11.18). Keverprazan was superior to esomeprazole in terms of eradication rate in the per protocol set (P =0.0382). The eradication rates for patients resistant or non-resistant to clarithromycin were both numerically higher in the KEV group than the ESO group (83.45% vs. 76.98% for clarithromycin-resistance; 92.31% vs. 88.16% for clarithromycin-non-resistance). The incidence of adverse events was similar in the KEV and ESO groups (76.31% vs. 77.62%), with most adverse events (>90%) being mild in severity. No TEAEs led to death in either group. Keverprazan 20 mg twice daily, used as a component of bismuth quadruple therapy, provided effective H. pylori eradication and was non-inferior to an esomeprazole-based regimen. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • A green synthesis of Ag-NPs was performed using Anisosciadium seeds extract as a reducing agent, for the first time. • The synthesized Ag-NPs were applied as sensitive fluorescent nanosensors for the determination of esomeprazole and lansoprazole. • The proposed method depends on the quantitative and selective quenching of the native fluorescence of Ag-NPs by the studied drugs. • The developed method was successfully applied for analysis of the studied drugs in dosage forms and human plasma. • The excellent greenness and eco-friendliness of the designed approach were demonstrated using GAPI and AGREE metrics. This study introduces a novel and eco-friendly method for the spectrofluorimetric determination of two important anti-GERD drugs, esomeprazole and lansoprazole. The study depends on synthesis of silver nanoparticles from Anisosciadium seeds extract as a reducing agent, for the first time. The synthesized silver nanoparticles were characterized by applying various microscopic and spectroscopic methods, including Fourier Transform Infrared, High Resolution Transmission Electron Microscopy, Energy-Dispersive X-Ray Analysis, Dynamic Light Scattering technique, Ultraviolet–Visible spectrophotometry, and spectrofluorimetry. The produced silver nanoparticles demonstrated an emission band at 311 nm if excited at 222 nm, and showed powerful blue fluorescence when exposed to UV light. The obtained silver nanoparticles were employed as fluorescent nanoprobes for the determination of esomeprazole and lansoprazole spectrofluorimetrically, depending on their quenching of the native fluorescence of silver nanoparticles quantitatively. This study is the first spectrofluorimetric strategy for the determination of the investigated medications with the use of silver nanoparticles without the requirement for any pre-derivatization stages or large volumes of organic solvents. As investigated medications don't display native fluorescent characteristics; the importance of the presented method increases. The suggested study demonstrated excellent linearity over the ranges of 1.0–10.0 μg/mL and 0.1–1.0 μg/mL with detection limits of 0.17 μg/mL and 0.015 μg/mL for esomeprazole and lansoprazole, respectively. The presented study was employed for the determination of esomeprazole and lansoprazole in human plasma samples and dosage forms with low % relative standard deviation and high % recoveries values. Greenness profile of the suggested method was assessed utilizing two various metrics, including Green Analytical Procedure Index (GAPI) and Analytical GREENNESS metric approach (AGREE), verifying lower environmental impact of the method and excellent eco-friendliness. The proposed strategy was validated in accordance with International Council for Harmonization (ICH) Q2 (R2) guidelines. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs), which inhibit gastric acid secretion, are frequently prescribed to patients with Parkinson's disease (PD). Levodopa, the gold-standard treatment for PD, demonstrates enhanced solubility in acidic environments. Although PPIs increase gastric pH and may affect levodopa absorption, the effect of concomitant PPI use on levodopa pharmacokinetics in patients with PD remains unknown. This study aimed to investigate the effect of the concomitant use of esomeprazole, a PPI, on the pharmacokinetics of levodopa and carbidopa and clinical symptoms in patients with PD. We prospectively enrolled 40 patients with PD and compared the pharmacokinetics of levodopa and carbidopa and clinical symptoms before and two weeks after the concomitant use of esomeprazole. The plasma concentrations of levodopa 30 min after concomitant oral administration of levodopa and esomeprazole were significantly lower (4.92 ± 4.10 μmol/L) than those without concomitant esomeprazole use (6.26 ± 3.75 μmol/L; p = 0.027). The plasma concentrations of carbidopa showed no significant differences with respect to concomitant esomeprazole use. Significant elevation was recorded in all subscores of the Movement Disorder Society-sponsored revision of the Unified Parkinson's disease Rating Scale scores after concomitant use of esomeprazole. No significant differences were observed between Helicobacter pylori -negative and Helicobacter pylori -positive patients. Non-elderly patients (age ≤ 70 years) tended to be more susceptible to the effect of esomeprazole on levodopa pharmacokinetics and clinical symptoms. The unnecessary use of PPIs should be avoided in patients with PD, especially in non-elderly patients, to improve absorption of levodopa. • This study prospectively enrolled 40 patients with Parkinson's disease. • Concomitant use of esomeprazole reduced the plasma concentrations of levodopa. • Plasma concentrations of carbidopa were not significantly altered. • Presence or absence Helicobacter pylori infection did not affect the results. • Non-elderly patients tended to be more susceptible to the effect of esomeprazole. [ABSTRACT FROM AUTHOR]

(1) Background: In critically ill cardiac patients, parenteral and enteral food and drug administration routes may be used. However, it is not well known how drug absorption and metabolism are altered in this group of adult patients. Here, we analyze drug absorption and metabolism in patients after cardiogenic shock using the pharmacokinetics of therapeutically indicated esomeprazole. (2) Methods: The pharmacokinetics of esomeprazole were analyzed in a consecutive series of patients with cardiogenic shock and controls before and after elective cardiac surgery. Esomeprazole was administered orally or with a nasogastric tube and once as an intravenous infusion. (3) Results: The maximum plasma concentration and AUC of esomeprazole were, on average, only half in critically ill patients compared with controls (p < 0.005) and remained lower even seven days later. Interestingly, esomeprazole absorption was also markedly compromised on day 1 after elective surgery. The metabolites of esomeprazole showed a high variability between patients. The esomeprazole sulfone/esomeprazole ratio reflecting CYP3A4 activity was significantly lower in critically ill patients even up to day 7, and this ratio was negatively correlated with CRP values (p = 0.002). The 5′-OH-esomeprazole and 5-O-desmethyl-esomeprazol ratios reflecting CYP2C19 activity did not differ significantly between critically ill and control patients. (4) Conclusions: Gastrointestinal drug absorption can be significantly reduced in critically ill cardiac patients compared with elective patients with stable cardiovascular disease. The decrease in bioavailability indicates that, under these conditions, any vital medication should be administered intravenously to maintain high levels of medications. After shock, hepatic metabolism via the CYP3A4 enzyme may be reduced.

Hae Won Lee,1,2 Woo Youl Kang,1,2 Wookjae Jung,1,2 Mi-Ri Gwon,1,2 Kyunghee Cho,3 Young-Ran Yoon,1,2 Sook Jin Seong1,2 1Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea; 2Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea; 3Analytical Research Division, Biocore Co. Ltd., Seoul, 08511, Republic of KoreaCorrespondence: Young-Ran Yoon, Department of Molecular Medicine, School of Medicine, Kyungpook National University, 130 Dongdeok-Ro, Jung-gu, Daegu, 41944, Republic of Korea, Tel +82 53-420-4950, Fax +82 53-420-5218, Email yry@knu.ac.kr Sook Jin Seong, Department of Clinical Pharmacology, School of Medicine, Kyungpook National University, 130 Dongduk-Ro, Jung-gu, Daegu, 41944, Republic of Korea, Tel +82 53-200-6351, Fax +82 53-420-5218, Email wintersj@knu.ac.krBackground: YYD601 was developed as a novel dual delayed release (DDR) formulation of esomeprazole to prolong the plasma esomeprazole concentration and extend the duration of acid suppression.Purpose: The pharmacokinetic (PK) and pharmacodynamics (PD) characteristics of YYD601 after single and multiple oral administrations were investigated in healthy Korean adults under fasting and fed conditions, and compared with the original esomeprazole capsule.Methods: In the single-center, randomized, open-label, parallel-design, two-period study, thirty two volunteers were enrolled into four dosing groups, including esomeprazole 40-mg (group A), YYD60130-mg (group B), YYD601 40-mg (group C), and YYD601 60-mg (group D) once daily for 5 days. Blood samples were collected for PK analysis, before and up to 24 h after dosing. For PD characteristics of YYD601, the percentages of time with intragastric pH > 4 over a 24-h period and during night-time following multiple oral administrations were evaluated.Results: A total of 27 subjects completed the study. YYD601 showed a dual-peak PK profile under fasting condition, with delayed Tmax, compared with conventional formulation. There were no significant differences in the AUC values adjusted for dose between the three YYD601 dosage groups and the conventional esomeprazole 40 mg. The esomeprazole AUC following single and multiple administration decreased with food intake by approximately 33%. YYD601 showed a linear pharmacokinetic profile in the dose range studied. There was no statistically significant difference in increase in mean percentage of time with intragastric pH > 4 for 24-hour and during night-time between the three different doses of YYD601 and the conventional formulation. The treatments were well-tolerated during the study and no serious adverse events were observed.Conclusion: YYD601 30 mg has a comparable effect on gastric acid inhibition as conventional esomeprazole 40 mg following once daily oral administration. Single and multiple oral dosing of YYD601 up to 60 mg were safe and well-tolerated throughout the study.Clinical Trial Registry: http://clinicaltrials.gov, NCT03558477 (date of registration: June 15, 2018; study period: between October 2017 and February 2018).Keywords: esomeprazole, dual delayed release, pharmacokinetics, pharmacodynamics

Abstract Background The present work describes the development and validation of a new, specific, accurate, and precise stability-indicating RP-HPLC method for the simultaneous estimation of Esomeprazole (ESP) and Naproxen (NAP) in modified-release bi-layer tablet dosage form. Analytical Quality by Design concept was implemented through the method development exercise to establish the robustness of the method. Results Method development was performed on C18, 250 × 4.6 mm ID, and 5 µm particle size column with 10 µl injection volume using a photodiode array (PDA) detector to monitor the detection at 280 nm. The mobile phase consisted of the buffer: methanol at a ratio of 50: 50 (v/v), and the flow rate was maintained at 1.5 ml/min, and the column oven temperature was maintained at 30 °C. The retention times for NAP and ESP were found 5.9 ± 0.1 and 8.9 ± 0.1 min, respectively. The method was validated in terms of system suitability, specificity, accuracy, linearity, precision, and solution stability. Linearity was observed over the range of concentration 8–12 µg/ml for ESP and 200–300 µg/ml for NAP, and the correlation coefficient (R 2) was found excellent > 0.999. The method was specific to ESP and NAP, and the peak purity was found 99.97% for ESP and 100.00% for NAP. The method was precise and had %RSD less than 2. Recovery study for accuracy with placebo was found in the range of 99.63–100.36% for ESP and 99.91–100.43% for NAP. Conclusion This proposed fast, reliable, cost-effective method can be used as a quality control tool for the simultaneous determination of Esomeprazole and Naproxen in routine laboratory analysis. Graphical Abstract

This study was conducted to evaluate and to compare the clinical, hemato-biochemical and endoscopic aspects of gastropathy in dogs treated with meloxicam alone or incombination with esomeprazole and misoprostol. Twenty baladi healthy dogs were included in the experimental study. Dogs were divided into four groups each group consisting of five animals; Group I (control group), the group that does not receive any medication. Meloxicam treated groups divided into: Group II which received meloxicam at a dose of 0.2 mg/kg BWT per OS /24 hr. Group III animals received the same previous dose of meloxicam and esomeprazole at a dose of 1mg/kg BWT per OS /24 hr. Group IV animals received the same dose of meloxicam and misoprostol 3μg /kg BWT per OS tid. Upon drug administration, dogs were kept under observation for 14 consecutive days. Clinical and hemato-biochemical analysis were evaluated across time (T0, T3, T7, T10 and T14). The image analysis of the gastroscopic examination was evaluated across time (T0, T7 and T14), endoscopic examinations were applied to all animals in four groups at three time points (T0, T7, and T14), endoscopic lesions were scored by use of a 5-point scale. Clinically, the most common clinical sings in dogs with Meloxicam induced- gastropathy were inappetence to anorexia, hematemesis, melena, abdominal pain and weakness, the specific endoscopic lesions of gastropathy were gastric erosion, hemorrhage and ulcers. Serum gastrin concentration is a biochemically sensitive indicator of gastropathy. The overall results concluded that meloxicam-induced gastropathy was more severe in group II compared to groups III and group IV. The proton pump inhibitor (esomeprazole) was more effective and better tolerated than misoprostol.

BackgroundProton 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.MethodsThis 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.ResultsThe 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).ConclusionUsing a large-scale data cohort analysis consisting of 50 million Koreans, tegoprazan did not induce higher hepatotoxicity compared with the six conventional PPIs.

Background: A high-dose proton pump inhibitor (PPI)-amoxicillin dual therapy has been investigated for treatment of patients with Helicobacter pylori (H. pylori) infection. Currently, the efficacy of this dual therapy remains inconclusive, with controversial findings from various single-center clinical trials. Objectives: To assess the efficacy and safety of high-dose dual therapy (HDDT) compared with the bismuth-containing quadruple therapy (BQT) in treatment-naive patients with H. pylori infection. Design: A multicenter, open-label, randomized controlled clinical trial. Methods: Three hundred and forty treatment-naïve patients with H. pylori infection were prospectively recruited from seven participating hospitals. The enrolled patients were randomized into one of two treatment groups: the HDDT group (esomeprazole, 20 mg four times daily; amoxicillin, 750 mg four times daily) and the BQT group (esomeprazole, 20 mg, twice daily; bismuth potassium citrate, 600 mg, twice daily; amoxicillin, 1 g, twice daily; metronidazole, 400 mg, four times daily). The primary outcome was eradication rate, and secondary outcomes were safety and patient compliance. Results: The eradication rates in the HDDT group versus the BQT group were 86.47% versus 87.06% on intention-to-treat (ITT) analysis, 91.88% versus 92.50% on modified ITT (MITT) analysis, and 91.77% versus 93.04% on per-protocol (PP) analysis, with no significant differences between the two groups. The patient compliance rates in the HDDT group versus the BQT group were 97.02% versus 95.86%, and no significant difference was found between the two groups. Notably, the HDDT group exhibited significantly lower incidence in the drug-induced adverse events (AEs) compared to the BQT group (16.67% versus 47.94%). Conclusion: HDDT is equally efficacious in eradicating H. pylori infection and resulted in good patient compliance and safety compared with BQT. These findings provide evidence in support of HDDT as a first-line treatment for H. pylori infection. Registration: This clinical trial was registered at The Chinese Clinical Trial Registry (trial registration number: ChiCTR2000039096). [ABSTRACT FROM AUTHOR]

Summary: The effects of polymorphisms in CYP3A4 (20230G > A), CYP3A5 (6986A > G), ABCB1 (1236C > T, 2677G > T/A, 3435C > T), ABCG2 (421C > A), and ABCC2 (-24C > T) on the area under the concentration–time curve (AUC) of osimertinib in 23 patients with non-small cell lung cancer were investigated. Blood sampling was performed just prior to and at 1, 2, 4, 6, 8, 12, and 24 h after osimertinib administration at the steady-state on day 15 after beginning therapy. The osimertinib AUC0-24 was significantly correlated with age (P = 0.038), serum albumin (P = 0.002), and serum creatinine (P = 0.012). Additionally, there were significant differences in the AUC0-24 of osimertinib among the groups administered vonoprazan, histamine 2-receptor antagonists or esomeprazole, and no acid suppressants (P = 0.021). By contrast, there were no significant differences in the AUC0-24 of osimertinib between genotypes of CYP3A4/5 or ABC transporters. Furthermore, there were no significant differences in the AUC0-24 of osimertinib between patients with diarrhea, skin rash, or hepatotoxicity and those without these conditions. In multivariate analysis, only serum albumin value was an independent factor predicting the AUC0-24 of osimertinib. Analysis of CYP3A4/5 and ABC transporter polymorphisms before osimertinib therapy may not predict the efficacy or side effects of osimertinib. The lower serum albumin values were associated with an increase in the AUC0-24 of osimertinib; however, further studies are needed to assess the factors contributing to the interindividual variability of osimertinib pharmacokinetics. [ABSTRACT FROM AUTHOR]

Background : Increasing antibiotic-resistant Helicobacter pylori (H. pylori) strains complicate efforts to eradicate infection. In regions with high dual resistance to both clarithromycin and metronidazole, bismuth quadruple therapy is recommended. But, with lack of easy availability of bismuth, the (non-bismuth) concomitant and sequential regimens are used commonly as first-line therapy. Recent reports indicate suboptimal results with sequential therapy in such regions. We aimed to compare the efficacy of concomitant therapy vs. sequential therapy in the eradication of H. pylori in a region with high antibiotic resistance rates, and to compare adherence rates and adverse events with the regimens. Methods: One hundred and twenty-four consecutive H. pylori–infected patients (diagnosed using rapid urease test or urea breath test) were randomized to receive sequential or concomitant therapy for 10 days each. Four weeks after treatment completion, urea breath test was done to confirm eradication of the infection. Cure rates were compared between the two regimens and note was made of adherence rates and adverse events. Results: Concomitant therapy showed a statistically non-significant higher cure rate compared to sequential therapy in intention-to-treat (87.1% vs. 81.4%%, p = 0.46) and per-protocol (94.7% vs. 83.9%, p = 0.07) analyses. Both the regimens were well tolerated and showed similar adherence rates (p = 1.00) and incidence of adverse events (p = 0.44). Conclusion: In a region with high dual resistance, both concomitant and sequential therapy for H. pylori infection achieved eradication rates >80%, but concomitant therapy showed a statistically non-significant higher cure rate, with similar adherence and adverse event profiles. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease of unknown etiology. Currently, pirfenidone and nintedanib are the only FDA-approved drugs for the treatment of IPF and are now the standard of care. This is a significant step in slowing down the progression of the disease. However, the drugs are unable to stop or reverse established fibrosis. Several retrospective clinical studies indicate that proton pump inhibitors (PPIs; FDA-approved to treat gastroesophageal reflux) are associated with favorable outcomes in patients with IPF, and emerging preclinical studies report that PPIs possess antifibrotic activity. In this study, we evaluated the antifibrotic efficacy of the PPI esomeprazole when combined with pirfenidone in vitro and in vivo. In cell culture studies of IPF lung fibroblasts, we assessed the effect of the combination on several fibrosis-related biological processes including TGFβ-induced cell proliferation, cell migration, cell contraction, and collagen production. In an in vivo study, we used mouse model of TGFβ-induced lung fibrosis to evaluate the antifibrotic efficacy of esomeprazole/pirfenidone combination. We also performed computational studies to understand the molecular mechanisms by which esomeprazole and/or pirfenidone regulate lung fibrosis. We found that esomeprazole significantly enhanced the anti-proliferative effect of pirfenidone and favorably modulated TGFβ-induced cell migration and contraction of collagen gels. We also found that the combination significantly suppressed collagen production in response to TGFβ in comparison to pirfenidone monotherapy. In addition, our animal study demonstrated that the combination therapy effectively inhibited the differentiation of lung fibroblasts into alpha smooth muscle actin (αSMA)-expressing myofibroblasts to attenuate the progression of lung fibrosis. Finally, our bioinformatics study of cells treated with esomeprazole or pirfenidone revealed that the drugs target several extracellular matrix (ECM) related pathways with esomeprazole preferentially targeting collagen family members while pirfenidone targets the keratins. In conclusion, our cell biological, computational, and in vivo studies show that the PPI esomeprazole enhances the antifibrotic efficacy of pirfenidone through complementary molecular mechanisms. This data supports the initiation of prospective clinical studies aimed at repurposing PPIs for the treatment of IPF and other fibrotic lung diseases where pirfenidone is prescribed. [ABSTRACT FROM AUTHOR]

Background: The Accelerating Innovation for Mothers (AIM) project established a database of candidate medicines in research and development (R&D) between 2000 and 2021 for five pregnancy-related conditions, including pre-eclampsia. In parallel, we published target product profiles (TPPs) that describe optimal characteristics of medicines for use in preventing/treating pre-eclampsia. The study objective was to use systematic double screening and extraction to identify all candidate medicines being investigated for pre-eclampsia prevention/treatment and rank their potential based on the TPPs.Methods: Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched (Jan-May 2021). The AIM database was screened for all candidates being investigated for pre-eclampsia. Candidates in clinical development were evaluated against nine prespecified criteria from TPPs identified as key for wide-scale implementation, and classified as high, medium or low potential based on matching to the TPPs. Preclinical candidates were categorised by product type, archetype and medicine subclass.Results: The AIM database identified 153 candidates for pre-eclampsia. Of the 87 candidates in clinical development, seven were classified as high potential (prevention: esomeprazole, L-arginine, chloroquine, vitamin D and metformin; treatment: sulfasalazine and metformin) and eight as medium potential (prevention: probiotic lactobacilli, dalteparin, selenium and omega-3 fatty acid; treatment: sulforaphane, pravastatin, rosuvastatin and vitamin B3). Sixty-six candidates were in preclinical development, the most common being amino acid/peptides, siRNA-based medicines and polyphenols.Conclusions: This is a novel, evidence-informed approach to identifying promising candidates for pre-eclampsia prevention and treatment - a vital step in stimulating R&D of new medicines for pre-eclampsia suitable for real-world implementation. [ABSTRACT FROM AUTHOR]

Context • The frequency of gastric-cancer (GC) diagnosis has been increasing in recent years and often has no obvious symptoms at an early stage. Upon clinical diagnosis of early GC (EGC), surgical treatment is generally recommended but as an invasive operation, surgical resection can’t avoid postoperative gastrointestinal dysfunction (GID) and other problems. Objective • The study intended to evaluate the clinical benefits for EGC patients of auricular point-pressing with beans, combined with esomeprazole magnesium (EM), for relieving gastrointestinal dysfunction (GID) after endoscopic submucosal dissection (ESD), aiming to provide accurate and effective reference opinions for future clinical treatment. Design • The research team designed a retrospective analysis. Setting • The study took place at the Jiangsu Province Hospital of Chinese Medicine in Nanjing, Jiangsu, China. Participants • Participants were 78 EGC patients who underwent ESD at the hospital between January 2019 and January 2021 and who had developed postoperative GID. Intervention • Thirty-seven patients chose to receive routine EM treatment, and they served as a control group. 41 patients chose to receive auricular point-pressing with bean plus EM intervention, and they served as a intervention group. Outcome Measures • At baseline and postintervention, the research team measured the levels of serum motilin (MOT), substance P (SP), prealbumin (PAB), transferrin (TF), and albumin (ALB). They also recorded the time of intestinal peristalsis recovery, first exhaust, first defecation, normal food intake, and resolution of abdominal distension symptoms. Finally, they counted the incidence of adverse events during treatment. Results • The levels of MOT, SP, PAB, TF, and ALB significantly changed between baseline and postintervention in both groups (P < .05). In the intervention group as compared to the control group postintervention, the decreases in the levels of MOT PAB, TF, and ALB and the increase in the SP level were significantly greater in the control group than those of the intervention group (all P < .05). In addition, the intervention group showed a shorter recovery time related to postoperative intestinal function and normal food intake and resolution of abdominal distension symptoms than did the control group (all P<.05), with a lower incidence of adverse events. Conclusions • Auricular point-pressing with beans plus EM can effectively alleviate the GID of EGC patients after ESD and help them to maintain normal gastrointestinal function, and its use is worth popularizing in clinical settings. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the bioequivalence of the newly developed delayed‐release oral suspension (test) 40 mg esomeprazole magnesium compared to its marketed counterpart (40 mg; reference) in healthy adult Chinese subjects. We conducted randomized, open‐label, two‐period, single‐dose, two‐way crossover trials over a 7‐day washout period, comprising a fasting trial and a fed trial. The subjects were administered the test or reference products in a 1:1 ratio at random throughout each period. Then, in the next session, they received the alternate products. Liquid chromatography‐tandem mass spectrometry and WinNonlin software were used to assess the bioequivalence of esomeprazole peak plasma concentration (Cmax) and area under the concentration–time curve (AUC). Overall, 33 subjects participated in the fasting trial and 42 subjects participated in the fed trial. Under both situations, the 90% confidence interval for the ratio of geometric means of Cmax, AUC0‐t, and AUC0‐∞ were within equivalence ranges (80%–125%). In these trials, no severe adverse events or protocol violations were observed. Moreover, when esomeprazole was administered while fed, the tmax was delayed, and both Cmax and AUC were reduced. The results of this research suggest that the test and reference formulations were bioequivalent under fasting and fed states. [ABSTRACT FROM AUTHOR]

Background. Studies have reported huge variations in the prescribing practice of warfarin. We carried out a clinical audit of warfarin use in an anticoagulation clinic of a tertiary care hospital. Methods. Patients receiving warfarin for at least 6 months were recruited and the following details were collected: demographics (age, body weight and gender); diagnoses; concomitant drugs. We calculated CHA₂DS₂-VASc, HASBLED and SAMe-TT2R2 scores for each study participant. Statins, proton pump inhibitors, carbamazepine and amiodarone were the concomitant drugs identified with potential drug interaction with warfarin in patients. Results. Two hundred and three patients were recruited. Almost one-third of the study population had poor anticoagulation status. CHA₂DS₂-VASc and HASBLED scores were the significant predictors of appropriate anticoagulation. Poor anticoagulation status was observed more commonly in the first 6 months following which improvements were seen. Nearly half-of the time abnormal PT-INR was observed to be either between 2 to 2.4 (for patients with heart valve replacements) or 1.5 to 1.9 (for other indications). Significant number of patients without any potentially interacting drugs was observed with higher risk of supra-therapeutic PT-INR. Conclusion. We observed a similar proportion of patients with adequate anticoagulation in our study participants as reported in other populations; and have identified categories at risk for poor anticoagulation. It is the need of the hour to develop in-house algorithm in compliance to international standards for dose titration of warfarin. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are often prescribed in association with clopidogrel and aspirin to patients with myocardial infraction (MI), but their effects on heart is controversial. The purpose of this study was to investigate the effects and potential mechanism of omeprazole (OME) and esomeprazole (ESO) in myocardial ischemia reperfusion (I/R) injury. In the present study, mice were treated with OME, ESO or vehicle for 3 weeks and then subjected to myocardial I/R or sham surgery. At 1 day after surgery, echocardiography was performed to access cardiac injury. Hematoxylin and eosin (H&E) staining was performed to evaluate cardiomyocyte morphology. The IL1β was evaluated by Immunohistochemistry (IHC). Elisa was used to detect cTnt content in serum. The expression of CD86, CD206, CHOP, ATF6, eIF2α and p eIF2α were determined by Western blot (WB). The result showed that ESO markedly improved the left ventricular ejection fraction (LVEF), shortening fraction (FS), suppressed inflammatory infiltration, endoplasmic reticulum stress (ERS) and decreased proinflammatory macrophages in I/R hearts, while OME had no significant effects on cardiac function, inflammation and ERS in the I/R heart. In conclusion, ESO but not OME pretreatment reduces the proportion of proinflammatory macrophages, inhibits endoplasmic reticulum stress, and alleviates I/R injury in mice, indicating that ESO maybe a more proper PPI than OME for application in I/R injury. • Compared with omeprazole, esomeprazole pretreatment could alleviate ischemia-reperfusioninjury and improve cardiac function in mice. • Esomeprazole reduced proinflammatory macrophages and inhibits endoplasmic reticulum stress in the ischemia-reperfusion heart. [ABSTRACT FROM AUTHOR]

Individualised medicine demands the formulation of pharmacotherapy in accordance with the characteristics of each patient's health condition, and paediatrics is one of the areas that needs this approach. The 3D printing of oral doses is one method for achieving customised medicine in paediatrics. In this work, pre-formulation studies were conducted to evaluate the viability of using specific raw materials to produce 3D printed dosage forms based on two active pharmaceutical ingredients (APIs), ondansetron and esomeprazole, which are important for therapeutic customisation in paediatrics. Pre-formulation studies were carried out by characterising the physical and chemical properties of selected raw materials, selected APIs and their mixtures, using analytical methods such as scanning electron microscopy (SEM), X-ray powder diffraction (X-RPD), simultaneous thermal analysis (STA) and differential scanning calorimetry (DSC). The flowability of powders, compatibility and stability studies were also performed. Among all the ingredients selected, the PVPs (K17, K25 and K90) had the best characteristics to incorporate both forms of Esomeprazole Mg in a formulation to produce extrudates. The results obtained validated the use of some selected raw materials for tablet manufacture by the 3D printing approach. [ABSTRACT FROM AUTHOR]

Esomeprazole is a proton pump inhibitor being investigated for treatment of preeclampsia. Esomeprazole pharmacokinetics during pregnancy are unknown. We used data from 10 pregnant participants with preterm preeclampsia, and 49 non‐pregnant participants to develop a population pharmacokinetic model of esomeprazole. A two‐compartment model described the data well. In pregnant participants after single dose, clearance was 42.2% (14.9–61.6%) lower compared to non‐pregnant, most likely due to inhibition of CYP2C19. In non‐pregnant participants after repeated dosing, clearance was 54.9% (48.2–63.5%) lower in extensive metabolizers and bioavailability was 33% (10.0–52.0%) higher compared to single dosing, which could be due to autoinhibition of CYP2C19. During pregnancy, the CYP2C19 autoinhibition effect with repeated dosing is expected to lead to much lower increase in exposure compared to non‐pregnant individuals, since CYP2C19 is already inhibited due to pregnancy. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor acidosis plays a major role in tumor aggressiveness, invasion and resistance, and it is considered an important target for novel anticancer strategies. In this work, we investigated the therapeutic efficacy of several proton pump inhibitors (Esomeprazole, Lansoprazole, Amiloride and Cariporide) to alter tumor acidity in prostate murine cancer models. The in vitro results showed a moderate toxicity for Esomeprazole that was selected for the successive in vivo studies. However, the in vivo studies highlighted the lack of response to Esomeprazole treatment in both subcutaneous and orthotopic PC3 prostate cancer models. Overall, MRI-based tumor pH imaging is a powerful tool for monitoring the in vivo response to treatment. The tumor microenvironment acidification confers treatment resistance; therefore, the interference with pH regulating systems is considered a new therapeutic strategy. In this study, two human prostate cancer cell lines, PC3 and LNCaP, have been treated in vitro with proton pump inhibitors (PPIs), namely Lansoprazole, Esomeprazole (V-ATPases-inhibitors), Cariporide, and Amiloride (NHE1-inhibitors). The cell viability and pH were assessed at several drug concentrations either at normoxic or hypoxic conditions. Since Esomeprazole showed the highest toxicity towards the PC3 cancer cells compared to LNCaP ones, athymic nude mice bearing subcutaneous or orthotopic PC3 tumors were treated with Esomeprazole (dose: 2.5 mg/kg body weight) for a period of three weeks—and tumor growth was monitored. MRI-CEST tumor pH imaging with Iopamidol was performed upon treatment at 3 h, 1 week (in combination with FDG-PET), and after 2 weeks for evaluating acute, early, and late responses. Although acute tumor pH changes were observed in vivo, long-term studies on both PC3 prostate cancer models did not provide any significant change in tumor acidosis or tumor growth. In conclusion, this work shows that MRI-CEST tumor pH imaging is a valuable tool for assessing the in vivo treatment response to PPIs. [ABSTRACT FROM AUTHOR]

Esomeprazole is an anti-gastric secretory Proton Pump Inhibitor (PPI), antiulcer. The present paper provides details of preparation of Esomeprazole loaded microspheres by solvent evaporation technique using ethyl cellulose EC22 matrix in order to investigate its effect on the encapsulation efficiency and drug release kinetics. The prepared formulation was characterized by FTIR spectroscopy, XRD powder, percentage of practical yield, drug loading, optical microscopy and in-vitro release studies in simulated gastric tract. In vitro dissolution studies showed that the release rate was largely affected by the microparticles’ characteristics. [ABSTRACT FROM AUTHOR]