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Gastroenterology Jan 2020
Topics: Aspirin; Double-Blind Method; Humans; Pantoprazole; Rivaroxaban
PubMed: 31704300
DOI: 10.1053/j.gastro.2019.10.032 -
Pharmacopsychiatry Mar 2020Polypharmacy including somatic medications such as proton pump inhibitors is a common phenomenon in psychiatric care. The aim of this study was to evaluate the...
BACKGROUND
Polypharmacy including somatic medications such as proton pump inhibitors is a common phenomenon in psychiatric care. The aim of this study was to evaluate the pantoprazole effects on clozapine metabolism.
METHODS
A large therapeutic drug-monitoring database containing plasma concentrations of CLZ was analyzed. The results were stratified into four groups: a non-smoking (n=250) and a smoking group (n=326), and two groups co-medicated with pantoprazole: non-smokers (n=26) and smokers (n=29). The analysis was based on the non-parametrical Mann-Whitney U test (M-W-U) with a significance level of 0.05.
RESULTS
Differences reached statistical significance for pharmacokinetic parameters between CLZ monotherapy and co-medication with pantoprazole neither in smokers nor in non-smokers (p>0.05 for M-W-U in pairwise comparisons). In patients with clozapine monotherapy, smokers had a higher daily dosage of CLZ compared to non-smokers (mean dosage 363±181 vs. 291±145 mg/day, p<0.001 for M-W-U).
CONCLUSIONS
Adding pantoprazole to an ongoing treatment with clozapine does not alter the metabolism of clozapine to a significant extent.
Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Databases, Factual; Drug Interactions; Drug Monitoring; Female; Humans; Male; Middle Aged; Pantoprazole; Proton Pump Inhibitors; Smokers; Young Adult
PubMed: 31614374
DOI: 10.1055/a-1021-8827 -
The Journal of Pediatrics Jul 2018
Topics: Body Weight; Child; Humans; Obesity; Pantoprazole
PubMed: 29680472
DOI: 10.1016/j.jpeds.2018.03.001 -
Gastroenterology Sep 2019Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial.
METHODS
We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up.
RESULTS
There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant.
CONCLUSIONS
In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.
Topics: Aged; Aspirin; Cardiovascular Diseases; Double-Blind Method; Drug Administration Schedule; Enterocolitis, Pseudomembranous; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Pantoprazole; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prospective Studies; Proton Pump Inhibitors; Risk Assessment; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome
PubMed: 31152740
DOI: 10.1053/j.gastro.2019.05.056 -
Journal of Cancer Research and... Apr 2022This study aimed to explore the role of pantoprazole (PPZ) in affecting the sensitivity of cervical cancer (CC) cells to cisplatin.
AIM
This study aimed to explore the role of pantoprazole (PPZ) in affecting the sensitivity of cervical cancer (CC) cells to cisplatin.
METHODS
HeLa and CaSki cells were exposed to cisplatin and/or PPZ treatment. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation, flow cytometry, wound healing, and transwell assays were performed to detect cell viability, proliferation, apoptosis, migration, and invasion of CC cells, respectively. Then, expressions of Beclin-1, LC3, and p62 were measured by western blot. Rapamycin (Rapa), acting as an autophagy activator, was applied to confirm the effect of autophagy on the sensitivity of CC cells to cisplatin.
RESULTS
Cisplatin treatment suppressed cell viability and proliferation and accelerated apoptosis of CC cells. Combination of cisplatin and PPZ or PPZ alone significantly inhibited cell viability, proliferation, migration, and invasion, and increased cell apoptosis of CC cells. Cisplatin enhanced expression levels of Beclin1 and LC3II/I, and reduced p62 expression. Combination of cisplatin and PPZ significantly decreased the expression levels of Beclin1 and LC3II/I, but increased p62 expression. The autophagy activator, Rapa, eliminated the inhibitory effects of the combination of cisplatin and PPZ on autophagy, and enhanced cell viability, but inhibited apoptosis of CC cells.
CONCLUSION
PPZ promotes the sensitivity of CC cells to cisplatin by inhibiting cisplatin-induced cell autophagy.
Topics: Antineoplastic Agents; Autophagy; Beclin-1; Cell Line, Tumor; Cisplatin; Female; Humans; Pantoprazole; Uterine Cervical Neoplasms
PubMed: 35645101
DOI: 10.4103/jcrt.jcrt_968_21 -
Acta Anaesthesiologica Scandinavica Oct 2019The long-term effects of stress ulcer prophylaxis with pantoprazole are unknown in ICU patients. We report 1-year mortality outcome in the Stress Ulcer Prophylaxis in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The long-term effects of stress ulcer prophylaxis with pantoprazole are unknown in ICU patients. We report 1-year mortality outcome in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial.
METHODS
In the SUP-ICU trial, acutely admitted adult ICU patients at risk of gastrointestinal bleeding were randomised to intravenous pantoprazole 40 mg vs placebo (saline) once daily during their ICU stay. We assessed mortality at 1 year and did sensitivity analyses according to the trial protocol and statistical analysis plan.
RESULTS
A total of 3261 of the 3291 patients with available data (99.1%) were followed up at 1 year after randomisation; 1635 were allocated to pantoprazole and 1626 to placebo. At 1 year after randomisation, 610 of 1635 patients (37.3%) had died in the pantoprazole group as compared with 601 of 1626 (37.0%) in the placebo group (relative risk, 1.01; 95% confidence interval 0.92-1.10). The results were consistent in the sensitivity analysis adjusted for baseline risk factors and in those of the per-protocol population. We did not observe heterogeneity in the effect of pantoprazole vs placebo on 1-year mortality in the predefined subgroups, that is, patients with and without shock, mechanical ventilation, liver disease, coagulopathy, high disease severity (SAPS II > 53) or in medical vs surgical ICU patients.
CONCLUSION
We did not observe a difference in 1-year mortality among acutely admitted adult ICU patients with risk factors for gastrointestinal bleeding allocated to stress ulcer prophylaxis with pantoprazole or placebo during the ICU stay. (The SUP-ICU trial was funded by Innovation Fund Denmark and others; ClinicalTrials.gov number, NCT02467621).
Topics: Aged; Anti-Ulcer Agents; Critical Care; Double-Blind Method; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Pantoprazole; Peptic Ulcer; Risk Factors; Simplified Acute Physiology Score; Treatment Outcome
PubMed: 31282567
DOI: 10.1111/aas.13436 -
International Journal of Clinical... May 1996This review summarizes the results of pharmacokinetic and pharmacodynamic drug interaction studies in man with pantoprazole, a new, selective proton pump inhibitor.... (Review)
Review
This review summarizes the results of pharmacokinetic and pharmacodynamic drug interaction studies in man with pantoprazole, a new, selective proton pump inhibitor. Various mechanisms have to be considered as causes for potential drug-drug interactions. Proton pump inhibitors (PPIs) in general may alter the absorption of drugs by increasing the intragastric pH. Due to the presence of an imidazole ring, the PPIs of the class of substituted benzimidazole sulfoxides may interfere with the metabolism of other drugs by altering the activity of drug metabolizing enzymes of the cytochrome P450 system, via either induction or inhibition. With the increasing use of PPIs, their interaction potential gains therapeutic importance as was the case with the first and second generation of H2-blockers (cimetidine and ranitidine, respectively). The enhanced selectivity of pantoprazole to the gastric H+/K(+)-ATPase characterizes the new PPI generation. In contrast to omeprazole, pantoprazole has a low potential to interact with the cytochrome P450 system in man. In the drug interaction studies conducted so far, substrates for all relevant cytochrome P450 families involved in the metabolism of drugs in man were investigated. Pantoprazole did not affect the pharmacokinetics or pharmacodynamics of antipyrine, caffeine, carbamazepine, diazepam, diclofenac, digoxin, ethanol, glibenclamide, a hormonal contraceptive (combination of levonorgestrel and ethinylestradiol), metoprolol, nifedipine, phenprocoumon, phenytoin, theophylline and warfarin in man. Pantoprazole also neither induced the metabolism of antipyrine or caffeine, nor increased urinary excretion of the induction markers D-glucaric acid and 6 beta-hydroxycortisol. Vice versa, the investigated drugs had no relevant influence on the pharmacokinetics of pantoprazole.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Benzimidazoles; Drug Interactions; Enzyme Inhibitors; Humans; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Sulfoxides
PubMed: 8793602
DOI: No ID Found -
International Journal of Molecular... Oct 2021Ischemia/reperfusion injury (IRI) in the kidney is the most common cause of acute renal dysfunction through different cell damage mechanisms. This study aimed to...
Ischemia/reperfusion injury (IRI) in the kidney is the most common cause of acute renal dysfunction through different cell damage mechanisms. This study aimed to investigate, on molecular basics for the first time, the effect of pantoprazole on renal IRI in rats. Different biochemical parameters and oxidative stress markers were assessed. ELISA was used to estimate proinflammatory cytokines. qRT-PCR and western blot were used to investigate the gene and protein expression. Renal histopathological examination was also performed. IRI resulted in tissue damage, elevation of serum levels of creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, IL-1β, up-regulation of NF-κB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it up-regulated the expression of the gene and down-regulated the expression of the -2 gene. Treatment of the injured rats with pantoprazole, either single dose or multiple doses, significantly alleviated IRI-induced biochemical and histopathological changes, attenuated the levels of proinflammatory cytokines, down-regulated the expression of NF-κB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins, and the gene, and up-regulated -2 gene expression. Moreover, treatment with pantoprazole multiple doses has an ameliorative effect that is greater than pantoprazole single-dose. In conclusion, pantoprazole diminished renal IRI via suppression of apoptosis, attenuation of the pro-inflammatory cytokines' levels, and inhibition of the intracellular signaling pathway MAPK (ERK1/2, JNK, p38)-NF-κB.
Topics: Animals; Apoptosis; Biomarkers; Cytokines; Disease Susceptibility; Gene Expression; Immunohistochemistry; Inflammation Mediators; Mitogen-Activated Protein Kinases; NF-kappa B; Oxidative Stress; Pantoprazole; Proto-Oncogene Proteins c-bcl-2; Rats; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; bcl-2-Associated X Protein
PubMed: 34639009
DOI: 10.3390/ijms221910669 -
Therapie Oct 2019Complications due to iron overload exert a problematic situation in patients with thalassemia. Proton pump inhibitors (PPIs) like pantoprazole are effective agents to... (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
Complications due to iron overload exert a problematic situation in patients with thalassemia. Proton pump inhibitors (PPIs) like pantoprazole are effective agents to reduce acid gastric acid secretion and perhaps to interrupt iron absorption in conditions with increased iron absorption. Our purpose was to study effects of pantoprazole addition to chelators on iron levels in patients with thalassemia major and intermedia.
METHODS
This randomized, controlled, and single center trial was performed on 60 patients with thalassemia major and intermedia in Amir Kabir hospital, Iran. Patients were randomized 1:1 to pantoprazole group (iron chelator plus pantoprazole) or control group (iron chelator) for 6 months. Serum ferritin was measured by ELISA. Iron content was measured by magnetic resonance imaging; heart T2*, and liver T2*.
RESULTS
After 6 months of treatment, a significant reduction was seen in serum ferritin levels in the pantoprazole group (1444±613μg/mL to 1197±956μg/mL; P<0.001). A further reduction was seen in patients with thalassmeia intermedia. There were no significant changes in myocardial T2* values in pantoprazole group compared to control group (23.6±7.3ms to 24.1±6.4ms). Compared to the control group, pantoprazole therapy had no effect on hepatic T2* value (9.7±2.3ms to 9.8±2.6ms). However, between-group difference was significant (P<0.05).
CONCLUSION
Pantoprazole therapy for 6 months has benefits for reducing serum ferritin in patients with thalassemia major and intermedia. Pantoprazole addition to iron chelators seems safe.
Topics: Adolescent; Adult; Child; Deferasirox; Deferiprone; Deferoxamine; Female; Ferritins; Humans; Iran; Iron Chelating Agents; Liver; Male; Middle Aged; Myocardium; Pantoprazole; Proton Pump Inhibitors; Single-Blind Method; Time Factors; Young Adult; beta-Thalassemia
PubMed: 30704764
DOI: 10.1016/j.therap.2018.11.013 -
Medical Oncology (Northwood, London,... Dec 2023Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to... (Randomized Controlled Trial)
Randomized Controlled Trial
Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to cytotoxic therapy. We conducted a phase I/II randomized controlled trial in adult patients with head and neck squamous cell carcinoma (HNSCC) planned for first-line palliative chemotherapy. Patients were randomized to chemotherapy + / - intravenous (IV) pantoprazole. The primary endpoint in phase I was to determine the maximum safe dose of intravenous pantoprazole, whereas it was progression-free survival (PFS) in phase II. The dose of IV pantoprazole established in phase I was 240 mg. Between Nov'18 and Oct'20, we recruited 120 patients in phase II, 59 on pantoprazole and 61 on the standard arm. Median age was 51 years (IQR 43-60), 80% were men. Systemic therapy was IV cisplatin in 22% and oral-metronomic-chemotherapy (OMC) in 78%. Addition of pantoprazole did not prolong PFS, which was 2.2 months (95% CI 2.07-3.19) in the pantoprazole arm and 2.5 months (95% CI 2.04-3.81, HR, 1.14; 95% CI 0.78-1.66; P = 0.48) in the standard arm. Response rates were similar; pantoprazole arm 8.5%, standard arm 6.6%; P = 0.175. Overall survival was also similar; 5.6 months (95% CI 4.47-8.51) in the pantoprazole arm and 5.4 months (95% CI 3.48-8.54, HR 1.06; 95% CI 0.72-1.57; P = 0.75) in the standard arm. Grade ≥ 3 toxicities were similar. Thus, pantoprazole 240 mg IV added to systemic therapy does not improve outcomes in patients with advanced HNSCC.
Topics: Adult; Male; Humans; Middle Aged; Female; Squamous Cell Carcinoma of Head and Neck; Pantoprazole; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Tumor Microenvironment
PubMed: 38129716
DOI: 10.1007/s12032-023-02234-z