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MethodsX Jun 2024Green analytical approaches are employed for the determination of active pharmaceutical ingredients, in conjunction with their impurities. Smart chemometric...
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.
PubMed: 38577411
DOI: 10.1016/j.mex.2024.102670 -
International Journal of Molecular... Jan 2024This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor-PPI) in resolving heartburn, reflux, and other symptoms and... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor-PPI) in resolving heartburn, reflux, and other symptoms and complications resulting from gastroesophageal reflux disease (GERD). The study followed PRISMA 2020 and was registered in PROSPERO (CRD42020206513). The search strategy used MeSH and free terms appropriately adapted for each database. Only randomized clinical trials (RCTs) were included. The Cochrane tool (RoB 2.0) was used to assess the risk of bias, and the certainty of evidence was rated using GRADE. Ten RCTs were included. Dexlansoprazole outperformed the placebo and other PPIs in the resolution of heartburn and reflux symptoms in patients with GERD, with benefits during and after treatment, especially in those with moderate and severe symptoms. The meta-analyses indicated that dexlansoprazole at doses of 30 and 60 mg had more 24 h heartburn-free days and nights compared to the placebo medications; no difference was reported between dexlansoprazole at doses of 30 and 60 mg in heartburn-free nights. A low bias risk and a moderate certainty of evidence were observed. This review confirms the therapeutic effect of dexlansoprazole (placebo-controlled) and its improvements in GERD symptoms compared to another PPI. However, the interpretation of the results should be carried out cautiously due to the small number of included studies and other reported limitations.
Topics: Humans; Dexlansoprazole; Gastroesophageal Reflux; Heartburn; Proton Pump Inhibitors; Treatment Outcome
PubMed: 38279248
DOI: 10.3390/ijms25021247 -
Annals of Medicine Dec 2023Esophageal adenocarcinoma incidence has increased significantly despite surveillance endoscopy for Barrett's esophagus (BE) and gastric acid supression medications. This...
INTRODUCTION
Esophageal adenocarcinoma incidence has increased significantly despite surveillance endoscopy for Barrett's esophagus (BE) and gastric acid supression medications. This prospective, cohort study's aims were to determine the long-term efficacy of proton-pump inhibitors twice daily (PPI-BID) with cryotherapy (CRYO) for complete ablation of BE.
MATERIALS AND METHODS
Consecutive BE patients were managed with a PPI-BID, CRYO ablation, follow-up protocol. Primary outcomes were to determine complete ablation rate of intestinal metaplasia (IM) or dysplasia/carcinoma, and factors affecting recurrence.
RESULTS
Sixty-two patients were enrolled: advanced disease (11%), low-grade or indefinite dysplasia (26%), non-dysplastic BE (63%). In 58 completing CRYO, eradication was confirmed in 100% on surveillance endoscopy. Adverse events (5%) were minor (mild pain 4%). IM recurred in 9% after a mean of 52 months, all successfully re-ablated. No second recurrence occurred. The primary predictor of recurrence was noncompliance with PPI-BID. BE or cardia IM recurred in 35% of those taking proton pump inhibitors once daily or less compared with 0% in those on PPI-BID or dexlansoprazole daily (<.001).
CONCLUSIONS
Minimizing acid reflux with at least PPI-BID combined with CRYO ablation appears to be the optimal cost-effective and safe BE treatment for any stage to minimize progression to adenocarcinoma by addressing both the stimulus that causes BE and the presence of goblet cells.
Topics: Humans; Barrett Esophagus; Proton Pump Inhibitors; Cryosurgery; Cohort Studies; Prospective Studies; Adenocarcinoma
PubMed: 37232568
DOI: 10.1080/07853890.2023.2191002 -
Biomedicines Apr 2023can be eradicated immediately via local application of single-dose medicament on endoscopic examination. In our previous report, "the eradication rate of intraluminal...
Intraluminal Therapy for Infection-Comparison of Medicament Containing Tetracycline, Metronidazole, and Bismuth versus Amoxicillin, Metronidazole, and Clarithromycin: A Randomized Controlled Study.
can be eradicated immediately via local application of single-dose medicament on endoscopic examination. In our previous report, "the eradication rate of intraluminal therapy for infection (ILTHPI) is 53.7% (51/95) using medicament containing amoxicillin, metronidazole, and clarithromycin". We aimed to evaluate the efficacy and adverse events of medicament containing tetracycline, metronidazole, and bismuth and to improve the efficacy of stomach acid control before ILTHPI. After usage of dexlansoprazole (60 mg b.i.d.) or vonoprazan (20 mg q.d.) for 3 days before ILTHPI, 103 of 104 (99.1%) symptomatic -infected treatment-naïve patients achieved levels of stomach pH ≥ 6. Patients were randomized to receive ILTHPI with medicaments containing tetracycline, metronidazole, and bismuth (Group A, = 52) or amoxicillin, metronidazole, and clarithromycin (Group B, = 52). The eradication rate of ILTHPI was similar between Group A (76.5%; 39/51) and Group B (84.6%, 44/52) ( = 0.427) and the adverse event was mild diarrhea (2.9%; 3/104). The eradication rate significantly increased from 53.7% (51/95) to 84.6% (44/52) after acid control ( = 0.0004) for Group B patients. The overall eradication rates of successful ILTHPI plus 7-day non-bismuth (Group A) or 7-day bismuth (Group B) oral quadruple therapy for ILTHPI failure patients were both excellent (96.1% for Group A and 98.1% for Group B).
PubMed: 37189702
DOI: 10.3390/biomedicines11041084 -
Pharmaceutics Mar 2023The COVID-19 pandemic has brought about unprecedented medical and healthcare challenges worldwide. With the continual emergence and spread of new COVID-19 variants, four...
The COVID-19 pandemic has brought about unprecedented medical and healthcare challenges worldwide. With the continual emergence and spread of new COVID-19 variants, four drug compound libraries were interrogated for their antiviral activities against SARS-CoV-2. Here, we show that the drug screen has resulted in 121 promising anti-SARS-CoV-2 compounds, of which seven were further shortlisted for hit validation: citicoline, pravastatin sodium, tenofovir alafenamide, imatinib mesylate, calcitriol, dexlansoprazole, and prochlorperazine dimaleate. In particular, the active form of vitamin D, calcitriol, exhibits strong potency against SARS-CoV-2 on cell-based assays and is shown to work by modulating the vitamin D receptor pathway to increase antimicrobial peptide cathelicidin expression. However, the weight, survival rate, physiological conditions, histological scoring, and virus titre between SARS-CoV-2 infected K18-hACE2 mice pre-treated or post-treated with calcitriol were negligible, indicating that the differential effects of calcitriol may be due to differences in vitamin D metabolism in mice and warrants future investigation using other animal models.
PubMed: 36986786
DOI: 10.3390/pharmaceutics15030925 -
Cureus Feb 2023The incidence and prevalence of eosinophilic esophagitis (EoE) are increasing in adults and children worldwide. Once thought primarily to affect children and young...
The incidence and prevalence of eosinophilic esophagitis (EoE) are increasing in adults and children worldwide. Once thought primarily to affect children and young adults, EoE is now recognized in all age groups. To our knowledge, this case study is the first known report of EoE diagnosed in an elderly man in Saudi Arabia. The 75-year-old patient presented with a chief complaint of dry mouth and mild heartburn symptoms. Further history inquiry disclosed that he experienced dysphagia occasionally. His endoscopy findings revealed signs associated with EoE, which was confirmed by biopsy showing marked infiltration of eosinophils (>30/hpf) in upper and lower esophagus. Following treatment with dexlansoprazole for eight weeks, the patient reported no further symptoms, and he remained in remission three months thereafter. Elderly patients with EoE may display atypical signs and symptoms and rarely have concomitant allergy; EoE should be considered in older patients especially those with dysphagia.
PubMed: 36909115
DOI: 10.7759/cureus.34705 -
Frontiers in Medicine 2022Proton pump inhibitors (PPIs) are acid suppressants that are frequently prescribed in many countries to reduce heartburn. A potassium-competitive acid blocker (P-CAB;...
BACKGROUND
Proton pump inhibitors (PPIs) are acid suppressants that are frequently prescribed in many countries to reduce heartburn. A potassium-competitive acid blocker (P-CAB; tegoprazan) was launched relatively recently that also inhibits gastric acid secretion. This study aimed to compare the hepatotoxicity of the six existing PPIs with P-CAB.
METHODS
This retrospective cohort study was conducted between January 2019 and December 2020 and included data from the total population of 50 million inhabitants in Korea. Propensity score (PS) matching was performed using 10 variables, and the differences in hepatotoxicity between P-CAB and the six PPIs were compared in a similar distribution. The primary endpoint was hepatotoxicity which included toxic liver disease, hepatitis, hepatic failure, liver transplantation, and other liver diseases.
RESULTS
The risk ratios (RR) of tegoprazan vs. the six PPIs (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) were all significant [RR: 0.70 (95% CI: 0.69-0.72), 0.81 (95% CI: 0.79-0.83), 0.61 (95% CI: 0.59-0.63), 1.17 (95% CI: 1.13-1.20), 0.61 (95% CI: 0.59-0.62), and 0.73 (95% CI: 0.71-0.75), respectively]. The risk ratio of tegoprazan vs. the six existing PPIs was 0.73 (95% CI: 0.72-0.75). The hazard ratios (HRs) of hepatotoxicity of the six PPIs to tegoprazan showed significantly higher values apart from omeprazole (HR: dexlansoprazole, 1.13; esomeprazole, 1.04; lansoprazole, 1.25; omeprazole, 0.77; pantoprazole, 1.26; rabeprazole, 1.15, respectively, and the six existing PPIs, 1.10).
CONCLUSION
Using a large-scale data cohort analysis consisting of 50 million Koreans, tegoprazan did not induce higher hepatotoxicity compared with the six conventional PPIs.
PubMed: 36714137
DOI: 10.3389/fmed.2022.1076356 -
Gut and Liver Jan 2023Tegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIMS
Tegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid breakthrough. To evaluate the pharmacodynamics of tegoprazan versus dexlansoprazole regarding nocturnal acid breakthrough in healthy subjects.
METHODS
In a randomized, open-label, single-dose, balanced incomplete block crossover study, 24 healthy male volunteers were enrolled and randomized to receive oral tegoprazan (50, 100, or 200 mg) or dexlansoprazole (60 mg) during each of two administration periods, separated by a 7- to 10-day washout period. Blood samples were collected for pharmacokinetic parameter analysis; gastric monitoring was performed for pharmacodynamic parameter evaluation.
RESULTS
All 24 subjects completed the study. Average maximum plasma concentration, area under the plasma concentration-time curve, and mean time with gastric pH >4 and pH >6 for tegoprazan demonstrated dose-dependent incremental increases. All the tegoprazan groups reached mean pH ≥4 within 2 hours, whereas the dexlansoprazole group required 7 hours after drug administration. Based on pharmacodynamic parameters up to 12 hours after evening dosing, 50, 100, and 200 mg of tegoprazan presented a stronger acid-suppressive effect than 60 mg of dexlansoprazole. Moreover, the dexlansoprazole group presented a comparable acid-suppressive effect with the tegoprazan groups 12 hours after dosing.
CONCLUSIONS
All the tegoprazan groups demonstrated a significantly faster onset of gastric pH increase and longer holding times above pH >4 and pH >6 up to 12 hours after evening dosing than the dexlansoprazole group.
Topics: Humans; Male; Dexlansoprazole; Cross-Over Studies; Proton Pump Inhibitors; Benzene Derivatives
PubMed: 36317518
DOI: 10.5009/gnl220050 -
Neurogastroenterology and Motility Jan 2023The comparative efficacy and safety of medical therapies for gastro-esophageal reflux symptoms in endoscopy-negative reflux disease is unclear. We conducted a network... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The comparative efficacy and safety of medical therapies for gastro-esophageal reflux symptoms in endoscopy-negative reflux disease is unclear. We conducted a network meta-analysis to evaluate efficacy and safety of proton pump inhibitors (PPIs), histamine-2-receptor antagonists, potassium-competitive acid blockers (PCABs), and alginates in patients with endoscopy-negative reflux disease.
METHODS
We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to February 1, 2022. We included randomized controlled trials (RCTs) comparing efficacy of all drugs versus each other, or versus a placebo, in adults with endoscopy-negative reflux disease. Results were reported as pooled relative risks with 95% confidence intervals to summarize effect of each comparison tested, with treatments ranked according to P-score.
KEY RESULTS
We identified 23 RCTs containing 10,735 subjects with endoscopy-negative reflux disease. Based on failure to achieve complete relief of symptoms between ≥2 and <4 weeks, omeprazole 20 mg o.d. (P-score 0.94) ranked first, with esomeprazole 20 mg o.d. or 40 mg o.d. ranked second and third. In achieving adequate relief, only rabeprazole 10 mg o.d. was significantly more efficacious than placebo. For failure to achieve complete relief at ≥4 weeks, dexlansoprazole 30 mg o.d. (P-score 0.95) ranked first, with 30 ml alginate q.i.d. combined with omeprazole 20 mg o.d., and 30 ml alginate t.i.d. second and third. In terms of failure to achieve adequate relief at ≥4 weeks, dexlansoprazole 60 mg o.d. ranked first (P-score 0.90), with dexlansoprazole 30 mg o.d. and rabeprazole 20 mg o.d. second and third. All drugs were safe and well-tolerated.
CONCLUSIONS & INFERENCES
Our results confirm superiority of PPIs compared with most other drugs in treating endoscopy-negative reflux disease. Future RCTs should aim to better classify patients with endoscopy-negative reflux disease, and to establish the role of alginates and PCABs in achieving symptom relief in both the short- and long-term.
Topics: Adult; Humans; Gastrointestinal Agents; Rabeprazole; Dexlansoprazole; Heartburn; Network Meta-Analysis; Gastroesophageal Reflux; Proton Pump Inhibitors; Omeprazole; Endoscopy, Gastrointestinal; Alginates; Treatment Outcome
PubMed: 36153790
DOI: 10.1111/nmo.14469 -
International Journal of Molecular... Sep 2022Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+... (Review)
Review
Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+ ATPase which controls acid production. Introduced to the market in 1989, their use has increased rapidly worldwide and they are now among the top 10 most prescribed drugs in the United States. As of 2015, the FDA has already approved six drugs of this class (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole and rabeprazole). Recently, the risks and benefits of long-term PPI use were questioned and many studies indicated that their use should be carefully considered, especially in young patients, whose treatment with these drugs could last many years. Even greater concerns have been raised about a potential positive association between PPIs and osteoporotic fracture risk including the hip, spine and wrist. Although based on observational studies, there is substantial evidence associating the long-term use of PPIs and fracture. This relationship is only partially admitted due to the lack of consistent effects of PPIs on bone mineral density loss. Therefore, this narrative review aimed to discuss the recent findings pertaining to the risk of osteoporotic fracture associated with PPIs, in particular prolonged use, and to call for further research to elucidate the mechanisms associated with this bone fragility.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adenosine Triphosphatases; Antacids; Bone Density; Dexlansoprazole; Esomeprazole; Humans; Lansoprazole; Omeprazole; Osteoporotic Fractures; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; United States
PubMed: 36142643
DOI: 10.3390/ijms231810733