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Toxicology Letters Oct 2020Proton pump inhibitors (PPIs) have wide pleiotropic action in addition to their therapeutic potential in gastroesophageal reflux diseases. Conversely, recent reports...
Proton pump inhibitors (PPIs) have wide pleiotropic action in addition to their therapeutic potential in gastroesophageal reflux diseases. Conversely, recent reports revealed a significant incidence of toxic events of PPIs including nephritis, osteoporosis, and cardiac damage. Thus, the study was designed to reconcile the deceptive contraindications. The present investigation targeted to reveal the toxic impact of sub-acute and sub-chronic administration of pantoprazole (PPZ) with different concentrations (low dose 4 mg/kg, medium-dose 8 mg/kg and high dose 16 mg/kg once a day) on normal vascular endothelium and renal tissue of rats. Vascular endothelial dysfunction (VED) was estimated by the contractility of an isolated aortic ring, nitrite/nitrate concentration, oxidative stress, and integrity of the endothelium layer. Moreover, the renal abnormalities were further confirmed by an increased level of serum creatinine, blood urea nitrogen (BUN), the incidence of microproteinuria, and structural alteration. Sub-acute administration of PPZ treatment did not produce any toxicological impact on endothelium and renal tissue. Whereas, sub-chronic administration of PPZ treatment causes moderate VED and renal dysfunction in a dose-dependent manner. Sub-chronic treatment of PPZ also influences the mitigation of NO and elevation of oxidative stress. Collecting all the evidence, it concludes that decreased nitric oxide availability and increased levels of oxidative stress may be a possible underlying mechanism of causing VED and renal abnormalities from high-dose PPZ treatment.
Topics: Administration, Oral; Animals; Aorta, Thoracic; Cytokines; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Kidney; Lipid Peroxidation; Male; Nitrates; Nitrites; Pantoprazole; Proton Pump Inhibitors; Rats; Rats, Wistar; Vasodilation
PubMed: 32763312
DOI: 10.1016/j.toxlet.2020.07.031 -
Clinical Pharmacology in Drug... Oct 2022Ripretinib is a switch control KIT kinase inhibitor approved for treatment of adults with advanced gastrointestinal stromal tumors who received prior treatment with 3 or...
Ripretinib is a switch control KIT kinase inhibitor approved for treatment of adults with advanced gastrointestinal stromal tumors who received prior treatment with 3 or more kinase inhibitors, including imatinib. Ripretinib and its active metabolite (DP-5439) are cleared mainly via cytochrome P450 enzyme 3A4/5 (CYP3A4/5), and ripretinib solubility is pH-dependent, thus the drug-drug interaction potentials of ripretinib with itraconazole (strong CYP3A inhibitor), rifampin (strong CYP3A inducer), and pantoprazole (proton pump inhibitor) were each evaluated in open-label, fixed-sequence study designs. Overall, 20 participants received ripretinib 50 mg alone and with itraconazole 200 mg once daily, 24 participants received ripretinib 100 mg alone and with rifampin 600 mg once daily, and 25 participants received ripretinib 50 mg alone and with pantoprazole 40 mg once daily. Ripretinib exposure increased with concomitant itraconazole, with geometric least-squares (LS) mean ratios of ripretinib area under the concentration-time curve from 0 to ∞ (AUC ) and maximum observed concentration (C ) of 199% and 136%. Ripretinib exposure decreased with concomitant rifampin: geometric LS mean ratios for ripretinib AUC and C were 39% and 82%. Pantoprazole coadministration had no effect on ripretinib pharmacokinetics. No unexpected safety signals occurred. No dose adjustment is required for ripretinib coadministered with gastric acid reducers and strong CYP3A inhibitors; patients also receiving strong CYP3A inhibitors should be monitored more frequently for adverse reactions. Concomitant ripretinib use with strong CYP3A inducers should be avoided. Prescribers should refer to approved labeling for specific dose recommendations with concomitant use of strong and moderate CYP3A inducers.
Topics: Adult; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Therapy, Combination; Gastric Acid; Humans; Imatinib Mesylate; Itraconazole; Naphthyridines; Pantoprazole; Protein Kinase Inhibitors; Proton Pump Inhibitors; Rifampin; Urea
PubMed: 35560823
DOI: 10.1002/cpdd.1110 -
Cureus Mar 2023Introduction The global proton pump inhibitors (PPIs) market was valued at US$ 2.9 billion in 2020 and is expected to exhibit a compound aggregated growth rate of 4.30%...
Introduction The global proton pump inhibitors (PPIs) market was valued at US$ 2.9 billion in 2020 and is expected to exhibit a compound aggregated growth rate of 4.30% during the forecast period (2020-2027), as they are regularly prescribed for many gastrointestinal disorders, and the treatment usually lasts for a longer period. PPIs are usually combined with antiemetics and prokinetic drugs. The price of PPIs for the same combination varies a lot, which can lead to a lot of financial burden on the patients. Objective To evaluate the cost ratio and percentage cost variation of commonly used PPIs in various combinations. Methodology The cost of different brands of commonly used PPIs in combination with other drugs was analyzed in our study. A total of 21 different combinations (10 capsules/tablets for oral use) were tabulated by referring to the "Monthly Index of Medical Specialities" October-December 2021, and 1mg online pharmacy. The cost ratio and percentage cost variation for various brands of a particular strength and dosage form were calculated and compared. Cost ratio > 2 and cost variation > 100% were considered significant. Results The results show a huge variation (1788.88%) in costs of different brands with the highest being rabeprazole 20 mg and domperidone 10 mg (cost ratio: 18.88, percentage cost variation: 1788.88%) in oral formulation, followed by pantoprazole 40 mg and itopride 150 mg. The minimum cost ratio (1.35) and percentage cost variation (1.35%) is for pantoprazole 40 mg and levosulpiride 75 mg. Logistic regression analysis between the number of brands and percentage cost variation gives an R value of 0.0923. Conclusion There is a wide variation in the prices of PPIs available in the market, which can inadvertently increase the financial burden of therapy on patients. Physicians need to be made aware of these price differences so that they can choose the best available alternative for patients, which can help in increasing compliance with the prescribed drugs.
PubMed: 37065352
DOI: 10.7759/cureus.36112 -
Medicine Nov 2022Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy and safety of first-line therapy, the choice of individual PPIs or vonoprazan in the treatment of EE remains controversial. This study aimed to evaluate the efficacy and safety of vonoprazan and PPIs in healing esophageal mucosal injury in patients with EE.
METHODS
Relevant databases were searched to collect randomized controlled trials of proton pump inhibitors and vonoprazan in the treatment of reflux esophagitis up to December 2021. Studies on standard-dose PPIs or vonoprazan that were published in Chinese or English and assessed healing effects in EE were included in the analysis. Stata16.0 was used to conduct a network Meta-analysis to evaluate the efficacy and safety of the treatment.
RESULTS
A total of 41 literatures were included with 11,592 enrolled patients. For the endoscopic cure rate, all the PPIs and vonoprazan significantly improve compared to Placebo; Based on the surface under the cumulative ranking curve, Ilaprazole ranked first, followed by esomeprazole, vonoprazan, pantoprazole, lansoprazole, omeprazole, rabeprazole and placebo therapy ranked the last. For the rate of adverse events, there was no significant difference among all the PPIs, vonoprazan, and placebo.
CONCLUSIONS
Ilaprazole, esomeprazole and vonoprazan have more advantages in mucosal erosion healing, there was no significant difference in the comparative safety among all interventions.
Topics: Humans; Proton Pump Inhibitors; Esomeprazole; Network Meta-Analysis; Peptic Ulcer; Rabeprazole; Esophagitis, Peptic; Abdominal Injuries
PubMed: 36451489
DOI: 10.1097/MD.0000000000031807 -
BioMed Research International 2023Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the...
BACKGROUND
Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the goal of this study was to see if it caused bone loss through gastrin secretion.
METHODS
Forty male rats were divided into control, octreotide (Oct), pantoprazole (Pan), and pantoprazole plus octreotide (Pan+Oct) groups. Serum calcium, phosphorous, alkaline phosphatase, parathyroid hormone, and gastrin were measured before and three months after the treatment, and bone densitometry was examined. The rats' femoral bones were examined stereologically at the end of the investigation.
RESULTS
The Pan group had considerably greater levels of serum alkaline phosphatase, parathyroid hormone (PTH), and gastrin, but this was prevented in the presence of Oct, a gastrin secretion inhibitor. All parameters of femoral bone densitometry in the Pan group were significantly lower than the control after treatment which was considerably inhibited in the presence of Oct. Furthermore, when compared to the control and Oct groups, the rats in the Pan group had a lower trabecular volume, femur bone weight, and volume, as well lower number of osteocytes. The amount of osteoclasts, on the other hand, was much higher in the Pan group than in the other groups.
CONCLUSION
Overall findings revealed that pantoprazole caused bone loss, which could be prevented by adding octreotide. Because these detrimental effects were not detected in rats given both Oct and Pan, it was suggested that the effect of Pan on bone was produced by a hypergastrinemic condition.
Topics: Male; Animals; Rats; Pantoprazole; Gastrins; Alkaline Phosphatase; Octreotide; Bone Diseases, Metabolic; Parathyroid Hormone
PubMed: 37711876
DOI: 10.1155/2023/2594664 -
Trials Aug 2023Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use...
Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial.
BACKGROUND
Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes in patients with and without COVID-19 infection.
METHODS
The ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection.
DISCUSSION
Prophylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research.
TRIAL REGISTRATION
REVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023].
Topics: Humans; Proton Pump Inhibitors; Pantoprazole; Respiration, Artificial; Cohort Studies; Critical Illness; Venous Thromboembolism; COVID-19; Gastrointestinal Hemorrhage; Randomized Controlled Trials as Topic
PubMed: 37644556
DOI: 10.1186/s13063-023-07589-2 -
Arquivos de Gastroenterologia 2023•In eradication treatment of H. pylori gemifloxacin containing triple treatment regimen was as effective as bismuth containing quadruple treatment. •Drug adverse...
•In eradication treatment of H. pylori gemifloxacin containing triple treatment regimen was as effective as bismuth containing quadruple treatment. •Drug adverse effects were fewer and milder in the gemifloxacin group. •Since treatment period was shorter and pills to be taken were fewer compared to quadruple treatment, patient compliance was significantly higher in the gemifloxacin group. Background - After eradication of Helicobacter pylori (H. pylori) chronic gastritis will resolve, complications due to H. pylori infection and recurrence of infection will be prevented. Objective - To determine efficacy and safety of gemifloxacin containing treatment regimen in first line treatment of H. pylori with comparison to bismuth containing quadruple therapy. Methods - This retrospective study was conducted in a tertiary care university hospital between January 2018 and January 2021 with 410 participants who were diagnosed to have H. pylori infection with biopsies obtained during upper gastrointestinal system endoscopy. Patients were distributed into two groups according to their first-line treatment regimens. First group patients were treated with amoxicillin, gemifloxacin and pantoprazole and second group patients were treated with amoxicillin, metronidazole, bismuth subcitrate and pantoprazole for seven days. Results - Intention to treat and per protocol ratios for gemifloxacin containing regimen were 90.0% and 91.2%, while quadruple treatment has these ratios as 91.7% and 93.8% respectively. Treatment success rate in both regimens were similar. But adverse effects were lower and patient compliance were better in patients who had gemifloxacin containing treatment (P<0.001). Conclusion - Gemifloxacin containing treatment regimen is as effective as bismuth containing quadruple treatment regimen for H. pylori infection and patient compliance is better in this group. Gemifloxacin containing treatment regimens may be novel and effective alternatives for eradication of H. pylori infection.
Topics: Humans; Gemifloxacin; Helicobacter pylori; Bismuth; Pantoprazole; Retrospective Studies; Drug Therapy, Combination; Helicobacter Infections; Amoxicillin; Metronidazole; Treatment Outcome; Gastritis; Anti-Bacterial Agents; Proton Pump Inhibitors
PubMed: 37792765
DOI: 10.1590/S0004-2803.230302-23-51 -
Frontiers in Oncology 2021The effective and economical therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC) is still requested from patients, who are not available for...
The effective and economical therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC) is still requested from patients, who are not available for Lu-177 or Ra-223 treatment. Drug repurposing as a cost-effective and time-saving alternative to traditional drug development has been increasingly discussed. Proton pump inhibitors (PPIs) such as pantroprazole, which are commonly used as antacids, have also been shown to be effective in cancer chemoprevention induction of apoptosis in multiple cancer cell lines. Vitamin C is an essential micronutrient for human body, has been proposed as a potential anti-cancer agent. In this context, have we investigated the combination of vitamin C and pantoprazole for the management of metastatic castration-resistant prostate cancer (mCRPC). Six chosen human adenocarcinoma cell lines were used to investigate the influence of pantoprazole on the microenvironment of cancer cells (extracellular pH and production of exosomes). Tumor growth and tumor 18F-FDG uptake in PC3 xenografts were analyzed following varied treatment. Our Results have suggested that pantoprazole enhanced the cytotoxic activity of vitamin C by regulating pH values and production of exosomes in cancer cells. Moreover, the synergistic effect of pantoprazole and vitamin C was pH-dependent since pantoprazole was more effective at a slightly acidic pH. In vivo, the combined treatment using pantoprazole and vitamin C produced better therapeutic outcomes than treatment with vitamin C or pantoprazole alone, as demonstrated tumor growth and uptake of 18F-FDG. Therefore, we suggest that pantoprazole combined with vitamin C could be as a possible strategy to manage mCRPC.
PubMed: 34307134
DOI: 10.3389/fonc.2021.660320 -
The Journal of the Association of... Oct 2023: To evaluate the effectiveness of rabeprazole and other proton pump inhibitors (PPIs) in providing symptomatic relief in patients with varying severity of...
: To evaluate the effectiveness of rabeprazole and other proton pump inhibitors (PPIs) in providing symptomatic relief in patients with varying severity of gastroesophageal reflux disease (GERD). : In this multicenter retrospective study, electronic medical records (EMRs) of GERD patients prescribed with PPIs at two Indian clinics/hospitals were reviewed (2016-2020). Rabeprazole's effectiveness was assessed at different follow-up visits and compared with other PPIs. : Overall, 269 patients (moderate and severe GERD: 84.39%) were included in three groups, rabeprazole, pantoprazole, and esomeprazole groups. A significant proportion of patients experienced quick and complete symptomatic relief at visit 1 with rabeprazole compared to the baseline visit, which gradually increased till visit 4 for both daytime [ heartburn (38.78-93.88%; < 0.001)] and nocturnal symptoms [ sleep disturbances (62.92-97.75%; < 0.001)]. Rabeprazole provided quick relief at visit 1 when compared with pantoprazole for daytime heartburn (38.78 vs 5.56%; = 0.01), daytime epigastric pain (66.04 vs 12.12%; = 0.049), and nocturnal water brash (60.71 vs 16.13%; = 0.015), and when compared with esomeprazole for nocturnal nausea (82.61 vs 20.00%; = 0.013). Further, the proportion of patients exhibiting complete treatment response was relatively higher in the rabeprazole group (83.33%) than in the pantoprazole (62.07%) and esomeprazole (65.67%) groups at visit 4. : Rabeprazole was effective in providing quick and sustained relief for both daytime and nocturnal GERD symptoms in patients with moderate and severe GERD. Rabeprazole also demonstrated greater effectiveness when compared with pantoprazole and esomeprazole in reducing the severity of multiple GERD symptoms. : Lawate P, Jilawar N, Vyas K, Effectiveness of Rabeprazole and Other Proton Pump Inhibitors in Managing GERD with Varying Severity: A Retrospective, Real-world EMR-based Study (POWER GERD Study). J Assoc Physicians India 2023;71(10):37-44.
Topics: Humans; Proton Pump Inhibitors; Gastroesophageal Reflux; Rabeprazole; Retrospective Studies; Male; Female; Middle Aged; Severity of Illness Index; Adult; Pantoprazole; Esomeprazole; Treatment Outcome; Electronic Health Records
PubMed: 38716522
DOI: 10.59556/japi.71.0366 -
Endocrine, Metabolic & Immune Disorders... Feb 2023Prenatal period is a critical developmental phase that is sensitive to hormonal disruption by natural and/or exogenous hormones. Some pharmaceuticals frequently...
BACKGROUND
Prenatal period is a critical developmental phase that is sensitive to hormonal disruption by natural and/or exogenous hormones. Some pharmaceuticals frequently prescribed and used safely during pregnancy are shown to interact with the developmental programming of fetus, resulting in endocrine-related adverse effects.
OBJECTIVE
In this research, we aimed to determine the endocrine disrupting potential of paracetamol, indomethacin, alpha-methyldopa and pantoprazole which are frequently prescribed pharmaceuticals during pregnancy.
METHODS
In vitro aromatase inhibitory, estrogen receptor (ER) agonist/antagonist (E-Screen assay) and hormone biosynthesis modulatory effects (H295R steroidogenesis assay) of the selected pharmaceuticals were evaluated. Furthermore, their effects on viability of MCF-7/BUS and H295R cells were also evaluated by MTT assay.
RESULTS
None of the pharmaceuticals affected H295R cell viability. Only indomethacin reduced MCF-7/BUS cell viability at 100µM and 300µM. Among the tested pharmaceuticals, only paracetamol and indomethacin showed aromatase inhibitory activity with IC 50 values of 14.7 x 10 -5 M and 57.6 x 10 -5 M, respectively. Moreover, indomethacin displayed a biphasic ER agonist effect. ER antagonist effects of indomethacin and pantoprazole were confirmed by performing two stepped E-Screen assay. After the partial validation of the H295R steroidogenesis assay with forskolin and prochloraz, the effects of pharmaceuticals on synthesis of testosterone (T) and estradiol (E2) levels were tested. Alpha-methyldopa increased E2 at all tested concentrations and T at 1.48 and 4.4µM. Contrarily other tested pharmaceuticals did not affect steroidogenesis.
CONCLUSION
Present data suggest that all tested pharmaceuticals may have potential endocrine disrupting effect, which should be considered when used in pregnancy.
PubMed: 36843259
DOI: 10.2174/1871530323666230224145624