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Przeglad Gastroenterologiczny 2018Proton pump inhibitors therapy success in the treatment of gastroesophageal reflux disease (GERD) is a difficult task because the extent of mucosal damage has no...
INTRODUCTION
Proton pump inhibitors therapy success in the treatment of gastroesophageal reflux disease (GERD) is a difficult task because the extent of mucosal damage has no relation with the severity of the symptoms.
AIM
To establish the efficacy of pantoprazole treatment in patients with erosive reflux disease (ERD) and in those with non-erosive reflux disease (NERD), by assessing symptom relief and quality of life. Treatment duration and adverse events associated with pantoprazole treatment were analysed.
MATERIAL AND METHODS
This meta-analysis was based on three multicentre, prospective, open-label, phase IV trials conducted in Slovenia, Poland, and the Russian Federation. In total, 252 patients with GERD were included and treated with pantoprazole 40 mg once daily for 4 or 8 weeks, depending on the fulfilment of predefined healing criteria. Symptoms were assessed by patients on a scale from 0 to 3 and the quality of life on a rating scale from 1 to 10.
RESULTS
Forty-five percent of patients fulfilled the healing criteria after 4 weeks of treatment, and 70% of patients after 8 weeks of treatment. Patients who failed to reach the healing criteria reported significant reduction of symptoms severity. The response to 8-week treatment was significantly higher in patients with ERD (76%) when compared to patients with NERD (64%). Discontinuation of treatment after 4 weeks was not associated with worsening of symptoms and did not affect quality of life. Pantoprazole treatment was associated with improvement of symptoms and the quality of life of GERD patients over 8 weeks of treatment and showed that GERD patients with persisting symptoms benefit from prolonging treatment to 8 weeks. Treatment with pantoprazole 40 mg was very well tolerated - more than 90% of patients were without adverse events throughout the whole study and only 4 patients discontinued the treatment due to adverse events related to pantoprazole treatment.
CONCLUSIONS
Pantoprazole 40 mg was associated with complete relief of GERD-related symptoms in the majority of patients with ERD and NERD. Furthermore, the severity of symptoms was significantly reduced in patients without complete relief of symptoms. Pantoprazole also continuously improved the quality of life of GERD patients over 8 weeks of treatment and was very well tolerated throughout the whole study. Therefore, this meta-analysis suggests that pantoprazole 40 mg once daily is an effective and well-tolerated choice for providing symptom relief of patients with GERD.
PubMed: 29657605
DOI: 10.5114/pg.2018.74556 -
Clinical and Molecular Allergy : CMA 2019Proton pump inhibitors (PPIs) are drugs capable of blocking the gastric pump H,K-ATPase in order to inhibit gastric acid secretion. Omeprazole, lansoprazole,...
Proton pump inhibitors (PPIs) are drugs capable of blocking the gastric pump H,K-ATPase in order to inhibit gastric acid secretion. Omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole belong to PPIs category. Although PPIs have a good safety profile, allergic reactions to these molecules can occur. The real rate of hypersensitive reactions to PPIs is unknown. The aim of this retrospective study is to evaluate the rate of hypersensitive reactions to PPIs in patients admitted to our Unit between 2008 and 2013 with a history of drug hypersensitivity. From a database of 1229 patients (921 women, 308 men) with adverse drug reaction we extrapolated the data about PPI reactions. Twelve patients (10 female, 2 men) had a positive history for hypersensitive reaction to PPI. Pantoprazole was the most frequently PPI involved. Based on patient personal history in some cases we performed an oral challenge test for an alternative anti-acid drug and none of them had adverse reactions. According to our experience and according to the literature and pharmacovigilance reports, ADR caused by PPIs are ever increasing. Adverse reactions to these drugs are still under-reported; however, considering the frequency of their prescription worldwide, the risk of severe allergic events is low. Further studies are needed to provide clearer data on the real incidence and prevalence about this matter. This should be useful to help physician in choosing the molecule to prescribe and, in case of hypersensitivity, the alternative molecule to test, also considering the possible cross-reactivity.
PubMed: 30675130
DOI: 10.1186/s12948-019-0104-4 -
Pharmaceutics Feb 2023Pantoprazole is a model substance that requires dosage form adjustments to meet the needs of all patients. Pediatric pantoprazole formulations in Serbia are mostly...
Pantoprazole is a model substance that requires dosage form adjustments to meet the needs of all patients. Pediatric pantoprazole formulations in Serbia are mostly compounded as capsules (divided powders), while in Western Europe liquid formulations are more common. The aim of this work was to examine and compare the characteristics of compounded liquid and solid dosage forms of pantoprazole. Three syrup bases were used: a sugar-free vehicle for oral solution (according to USP43-NF38), a vehicle with glucose and hydroxypropyl cellulose (according to the DAC/NRF2018) and a commercially available SyrSpend Alka base. Lactose monohydrate, microcrystalline cellulose and a commercially available capsule filler (excipient II, composition: pregelatinized corn starch, magnesium stearate, micronized silicon dioxide, micronized talc) were used as diluents in the capsule formulations. Pantoprazole concentration was determined by the usage of the HPLC method. Pharmaceutical technological procedures and microbiological stability measurements were performed according to the recommendations of the EP10. Although dose appropriate compounding with pantoprazole is suitable using both liquid vehicles as well as solid formulations, chemical stability is enhanced in solid formulation. Nevertheless, according to our results, if liquid formulation is a pH adjusted syrup, it could be safely kept in a refrigerator for up to 4 weeks. Additionally, liquid formulations could be readily applied, while solid formulation should be mixed with appropriate vehicles with higher pH values.
PubMed: 36986577
DOI: 10.3390/pharmaceutics15030717 -
Clinical and Translational Science May 2022The C-pantoprazole breath test (PAN-BT) is a safe, noninvasive, in vivo CYP2C19 phenotyping probe for adults. Our objective was to evaluate PAN-BT performance in... (Clinical Trial)
Clinical Trial
The C-pantoprazole breath test (PAN-BT) is a safe, noninvasive, in vivo CYP2C19 phenotyping probe for adults. Our objective was to evaluate PAN-BT performance in children, with a focus on discriminating individuals who, according to guidelines from the Clinical Pharmacology Implementation Consortium (CPIC), would benefit from starting dose escalation versus reduction for proton pump inhibitors (PPIs). Children (n = 65, 6-17 years) genotyped for CYP2C19 variants *2, *3, *4, and *17 received a single oral dose of C-pantoprazole. Plasma concentrations of pantoprazole and its metabolites, and changes in exhaled CO (termed delta-over-baseline or DOB), were measured 10 times over 8 h using high performance liquid chromatography with ultraviolet detection and spectrophotometry, respectively. Pharmacokinetic parameters of interest were generated and DOB features derived using feature engineering for the first 180 min postadministration. DOB features, age, sex, and obesity status were used to run bootstrap analysis at each timepoint (T ) independently. For each iteration, stratified samples were drawn based on genotype prevalence in the original cohort. A random forest was trained, and predictive performance of PAN-BT was evaluated. Strong discriminating ability for CYP2C19 intermediate versus normal/rapid metabolizer phenotype was noted at DOB (mean sensitivity: 0.522, specificity: 0.784), with consistent model outperformance over a random or a stratified classifier approach at each timepoint (p < 0.001). With additional refinement and investigation, the test could become a useful and convenient dosing tool in clinic to help identify children who would benefit most from PPI dose escalation versus dose reduction, in accordance with CPIC guidelines.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Breath Tests; Child; Cytochrome P-450 CYP2C19; Genotype; Humans; Pantoprazole; Proton Pump Inhibitors
PubMed: 35099109
DOI: 10.1111/cts.13232 -
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 -
Cureus Sep 2019Proton pump inhibitors (PPIs) are amongst the most prescribed medications in the whole world due to their effectiveness and safety profile. However, doubts have arisen... (Review)
Review
Proton pump inhibitors (PPIs) are amongst the most prescribed medications in the whole world due to their effectiveness and safety profile. However, doubts have arisen about its safety in long term use and have been associated with an increased risk of developing gastric cancer. We aim to study if there is an association between chronic PPI use and the risk of gastric cancer. If this is true, we would like to know the duration of use at which the risk of cancer is high. We performed a literature review of relevant full articles present in the PubMed database that were published in the last five years. Articles that were in the English language and discussed the risk of gastric cancer with chronic PPI use in adult age groups (18 years and above) were evaluated. Only observational or interventional studies with more than 20,000 participants were considered. Two nationwide based studies were included in this review, the Cheung study, and the Brusselaers study. The Cheung study included a total of 63,397 individuals, where 153 cases developed gastric cancer. PPI users had a hazard ratio of 2.44 (95% confidence interval [CI] 1.42-4.20), and the risk of cancer increased with the duration of PPI use. The Brusselaers study included a total of 797,067 individuals, where 2,219 cases developed gastric cancer. The standardized incidence ratio of gastric cancer among PPI users was 3.38 (95% CI 3.23-3.53), and the risk of cancer increased with the duration of PPI use. Therefore, chronic PPI use is associated with an increase in the risk of gastric cancer. It might also be an independent risk factor for gastric cancer.
PubMed: 31523592
DOI: 10.7759/cureus.5563 -
Case Reports in Gastrointestinal... 2020Cannabinoid hyperemesis syndrome (CHS), associated with chronic cannabis use, presents with cyclic abdominal pain, nausea, and vomiting. With increasing use of...
INTRODUCTION
Cannabinoid hyperemesis syndrome (CHS), associated with chronic cannabis use, presents with cyclic abdominal pain, nausea, and vomiting. With increasing use of marijuana, the incidence of CHS is expected to increase. Most patients with CHS make frequent visits to the emergency room and are usually refractory to conventional treatment. We, therefore, present a case of CHS successfully treated with topical capsaicin application. . A 41-year-old female with a recent excess use of cannabis presented to the emergency department for evaluation of recurrent excruciating epigastric pain accompanied by severe nausea and vomiting. She had similar, milder symptoms a year ago and underwent endoscopic evaluation which was negative except for mild reflux esophagitis for which she was started on a proton pump inhibitor. On this presentation, basic laboratory workup, EKG, and CT scan of abdomen and pelvis were unremarkable. A detailed abdominal exam was only positive for mild epigastric tenderness. She was instructed to continue pantoprazole and pain medication and outpatient repeat esophagogastroduodenoscopy. The patient returned the next day with extreme retching, nausea, and vomiting and was admitted for further evaluation. Intravenous fluids, antiemetics, and morphine were started for pain control with no symptomatic improvement. A diagnosis of cannabis hyperemesis syndrome was made based on history of chronic marijuana use and otherwise negative workup. A trial of topical capsaicin, over the epigastric region, was tried that provided dramatic relief within 24 hours. Repeat endoscopic evaluation had no evidence of ulcers, celiac disease, or esophagitis. She was discharged on topical capsaicin and counselled on marijuana abstinence, with no return of symptoms.
CONCLUSION
Based on the dramatic resolution of symptoms with topical capsaicin, our case supports this promising intervention and provides an alternate approach to antiemetics and narcotics routinely used in patients with cannabis hyperemesis syndrome.
PubMed: 33294233
DOI: 10.1155/2020/8868385 -
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 -
Basic & Clinical Pharmacology &... Feb 2017Pantoprazole is a proton pump inhibitor that is commonly used in the treatment of peptic ulcer disease (PUD) and metabolized by cytochrome P450 (CYP) enzymes CYP2C19 and...
Pantoprazole is a proton pump inhibitor that is commonly used in the treatment of peptic ulcer disease (PUD) and metabolized by cytochrome P450 (CYP) enzymes CYP2C19 and CYP3A4. Pantoprazole is a substrate for multi-drug resistance protein 1 (MDR1). Single nucleotide polymorphisms (SNPs) in CYP2C19, CYP3A4 and MDR1 affect enzyme activity or gene expression of proteins and may alter plasma pantoprazole concentrations and treatment success in PUD. In this study, we aimed to investigate the association between genetic polymorphisms in CYP2C19, CYP3A4 and MDR1 and pharmacokinetics of pantoprazole and therapeutic outcome in patients with either Helicobacter pylori-associated [H.P.(+)]-PUD or [H.P.(+)]-gastritis. The plasma pantoprazole concentrations were determined by using an HPLC method at the third hour after a 40-mg tablet of pantoprazole administration in 194 newly diagnosed patients with either [H.P.(+)]-PUD or [H.P.(+)]-gastritis. Genotyping was performed by using PCR-RFLP and DNA sequencing. Among patients appearing for follow-up examination (n = 105), the eradication rate for H. pylori was 82.8% (n = 87). The median pantoprazole plasma concentrations in poor metabolizers (PM), rapid metabolizers (RM) and ultrarapid metabolizers (URM) were 2.07, 1.69 and 1.28 μg/ml, respectively (p = 0.04). CYP3A4*1G and *22 polymorphisms did not affect plasma pantoprazole concentrations and H. pylori eradication rate. The MDR1 genetic polymorphisms did not affect plasma pantoprazole concentrations. MDR1 3435CC-2677GG-1236CC haplotype carriers had lower H. pylori eradication rate (60%) than the remaining subjects (84.9%) while the difference was not statistically significant (p = 0.07). In conclusion, while CYP2C19 genetic polymorphisms significantly affected plasma pantoprazole concentrations, polymorphisms of CYP2C19, CYP3A4 and MDR1 did not affect H. pylori eradication rates.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; ATP Binding Cassette Transporter, Subfamily B; Administration, Oral; Adult; Biotransformation; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Monitoring; Female; Gastritis; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Male; Pantoprazole; Peptic Ulcer; Pharmacogenetics; Phenotype; Polymorphism, Single Nucleotide; Proton Pump Inhibitors; Treatment Outcome
PubMed: 27611887
DOI: 10.1111/bcpt.12667 -
JGH Open : An Open Access Journal of... Jul 2023There is limited research on the use of histamine-H2 receptor antagonists and proton pump inhibitors for treating COVID-19. We compare clinical outcomes between patients...
BACKGROUND AND AIM
There is limited research on the use of histamine-H2 receptor antagonists and proton pump inhibitors for treating COVID-19. We compare clinical outcomes between patients hospitalized with COVID-19 receiving famotidine or pantoprazole.
METHODS
This retrospective study included 2184 patients (famotidine: = 638, pantoprazole: = 727, nonuse: = 819) aged 18 years or older treated for COVID-19 from March 2020 to March 2021. Patients who received both famotidine and pantoprazole treatments were excluded. Multivariate logistic regression was used for the primary outcome, namely all-cause mortality, and the secondary outcomes, namely mechanical ventilation, vasopressor use, acute kidney injury, and gastrointestinal bleeding. The main predictor variable was the use of famotidine or pantoprazole. Covariates were demographics, chronic diseases, and symptoms.
RESULTS
As compared to nonuse, famotidine (OR: 0.30, 95% CI: 0.20-0.44, < 0.001) and pantoprazole (OR: 0.47, 95% CI: 0.33-0.66, < 0.001) were significantly associated with lower odds for all-cause mortality. Comparison of famotidine and pantoprazole showed that the former had lower odds for all-cause mortality (OR: 0.65, 95% CI:0.45-0.95, < 0.05), mechanical ventilation (OR: 0.38, 95% CI: 0.25-0.58, < 0.001), vasopressor use (OR: 0.33, 95% CI: 0.22-0.48, < 0.001), acute kidney injury (OR: 0.40, 95% CI: 0.30-0.54, < 0.001), and gastrointestinal bleeding (OR: 0.15, 95% CI: 0.08, 0.29, < 0.001).
CONCLUSIONS
Famotidine is associated with lower odds for all-cause mortality, mechanical ventilation, vasopressor use, acute kidney injury, and gastrointestinal bleeding as compared to pantoprazole in patients hospitalized with COVID-19. We recommend that clinicians consider the use of famotidine over pantoprazole for hospitalized COVID-19 patients. Future research with a clinical trial would be beneficial to further support such use of famotidine.
PubMed: 37496815
DOI: 10.1002/jgh3.12905