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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 -
Alimentary Pharmacology & Therapeutics Jan 2010Esomeprazole and pantoprazole are metabolized in the liver and the polymorphic CYP2C19 enzyme is involved in that process. This genetic polymorphism determines fast (70%... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Esomeprazole and pantoprazole are metabolized in the liver and the polymorphic CYP2C19 enzyme is involved in that process. This genetic polymorphism determines fast (70% of Caucasians), intermediate (25-30% of Caucasians) and slow (2-5% of Caucasians) metabolism of PPIs.
AIM
To compare the acid-inhibitory effects of esomeprazole 40 mg and pantoprazole 40 mg at 4, 24 and 120 h after oral administration in relation to CYP2C19 genotype and pharmacokinetics.
METHODS
CYP2C19*2, *3, *4, *5 and *17 genotypes were determined in healthy Helicobacter pylori-negative Caucasian subjects. 7 wt/wt, 7 wt/*2, 2 wt/*17, 2 *2/*17 and 1 *2/*2 were included in a randomized investigator-blinded cross-over study with esomeprazole 40 mg and pantoprazole 40 mg. Intragastric 24-h pH-monitoring was performed on days 0, 1 and 5 of oral dosing.
RESULTS
A total of 19 subjects (mean age 24 years, 7 male) completed the study. At day 1 and 5, acid-inhibition with esomeprazole was significantly greater and faster than with pantoprazole. Differences in acid-inhibition and pharmacokinetics between wt/wt and wt/*2 genotype were significant for pantoprazole at day 1 and 5.
CONCLUSIONS
Esomeprazole provides acid-inhibition faster than and superior to pantoprazole after single and repeated administration. The acid-inhibitory effect and the kinetics of pantoprazole are influenced by CYP2C19 genotype.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Anti-Ulcer Agents; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C19; Esomeprazole; Female; Gastric Acid; Gastric Acidity Determination; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Male; Monitoring, Physiologic; Pantoprazole; Polymorphism, Genetic; Time Factors; Treatment Outcome; Young Adult
PubMed: 19785625
DOI: 10.1111/j.1365-2036.2009.04150.x -
American Journal of Translational... 2019To investigate the effect of pantoprazole on acute lung and kidney injury with sepsis and its possible mechanism. Rats were randomly divided into six groups, the status...
To investigate the effect of pantoprazole on acute lung and kidney injury with sepsis and its possible mechanism. Rats were randomly divided into six groups, the status and lung wet/dry weight ratio were determined at various time points. Hematoxylin Eosin staining (HE) for pathological changes in the lungs and kidneys of rats with sepsis. Western blot (WB) and immunohistochemistry were used to detect the pulmonary surfactant protein A(SPA) and D(SPD). The levels of markers for kidney damage in serum and urine various time points were measured by ELISA. The apoptosis in lung and kidney tissue of rats were detected using TUNEL assay. Subsequently, the cell apoptosis of LPS-induced BEAS-2B and HK-2 cells after pantoprazole treatment were detected using flow cytometry. The levels of RHOA/ROCK signaling pathway proteins in the lung and kidney tissues and cells were detected using WB. Our results indicated that Pantoprazole could suppress the expression of inflammatory factors in the blood and alleviate pathological damage of lung and kidney tissues in rats with sepsis. Pantoprazole treatment could reduce apoptosis in lung and kidney tissues and inhibit cell apoptosis induced by LPS. In addition, pantoprazole can inhibit RHOA/ROCK signaling pathway proteins and the levels of inflammatory factors in LPS-induced BEAS-2B and HK-2 cells. Pantoprazole can improve the symptoms of acute lung and kidney injury in septic rats, which suggested that pantoprazole might be used to guide the treatment of sepsis.
PubMed: 31497234
DOI: No ID Found -
International Journal of Molecular... Jan 2023Proton-pump inhibitors (PPI), e.g., omeprazole or pantoprazole, are the most widely used drugs for various gastrointestinal diseases. However, more and more side...
Proton-pump inhibitors (PPI), e.g., omeprazole or pantoprazole, are the most widely used drugs for various gastrointestinal diseases. However, more and more side effects, especially an increased risk of infections, have been reported in recent years. The underlying mechanism has still not yet been fully uncovered. Hence, in this study, we analyzed the T cell response after treatment with pantoprazole in vitro. Pantoprazole preincubation reduced the production and secretion of interferon (IFN)-γ and interleukin (IL)-2 after the T cells were activated with phytohemagglutinin (PHA)-L or toxic shock syndrome toxin-1 (TSST-1). Moreover, a lower zinc concentration in the cytoplasm and a higher concentration in the lysosomes were observed in the pantoprazole-treated group compared to the untreated group. We also tested the expression of the zinc transporter Zrt- and Irt-like protein (Zip)8, which is located in the lysosomal membrane and plays a key role in regulating intracellular zinc distribution after T cell activation. Pantoprazole reduced the expression of Zip8. Furthermore, we measured the expression of cAMP-responsive element modulator (CREM) α, which directly suppresses the expression of IL-2, and the expression of the phosphorylated cAMP response element-binding protein (pCREB), which can promote the expression of IFN-γ. The expression of CREMα was dramatically increased, and different isoforms appeared, whereas the expression of pCREB was downregulated after the T cells were treated with pantoprazole. In conclusion, pantoprazole downregulates IFN-γ and IL-2 expression by regulating the expression of Zip8 and pCREB or CREMα, respectively.
Topics: Proton Pump Inhibitors; Pantoprazole; Interleukin-2; 2-Pyridinylmethylsulfinylbenzimidazoles; Zinc; T-Lymphocytes; Acids
PubMed: 36674704
DOI: 10.3390/ijms24021191 -
The Oncologist Jul 2018Using a randomized crossover design and continuous variables such as change in hearing threshold and biomarkers of acute renal injury as short-term endpoints, it was... (Randomized Controlled Trial)
Randomized Controlled Trial
Pantoprazole, an Inhibitor of the Organic Cation Transporter 2, Does Not Ameliorate Cisplatin-Related Ototoxicity or Nephrotoxicity in Children and Adolescents with Newly Diagnosed Osteosarcoma Treated with Methotrexate, Doxorubicin, and Cisplatin.
LESSONS LEARNED
Using a randomized crossover design and continuous variables such as change in hearing threshold and biomarkers of acute renal injury as short-term endpoints, it was determined that pantoprazole, an organic cation transporter 2 inhibitor, did not ameliorate cisplatin-associated nephrotoxicity or ototoxicity.Cystatin C is a robust method to estimate glomerular filtration rate in patients with cancer. Using a patient-reported outcome survey, all patients identified tinnitus and subjective hearing loss occurring "at least rarely" after cycle 1, prior to objective high-frequency hearing loss measured by audiograms.New therapies that improve outcome with less acute and long-term toxicity are needed.
BACKGROUND
Organic cation transporter 2 (OCT2), which is a cisplatin uptake transporter expressed on renal tubules and cochlear hair cells but not on osteosarcoma cells, mediates cisplatin uptake. Pantoprazole inhibits OCT2 and could ameliorate cisplatin ototoxicity and nephrotoxicity. Using a randomized crossover design, we evaluated audiograms, urinary acute kidney injury (AKI) biomarkers, and glomerular filtration rate (GFR) estimated from cystatin C (GFR) in patients receiving cisplatin with and without pantoprazole.
MATERIALS AND METHODS
Cisplatin (60 mg/m × 2 days per cycle) was administered concurrently with pantoprazole (intravenous [IV], 1.6 mg/kg over 4 hours) on cycles 1 and 2 or cycles 3 and 4 in 12 patients with osteosarcoma (OS) with a median (range) age of 12.8 (5.6-19) years. Audiograms, urinary AKI biomarkers, and serum cystatin C were monitored during each cycle.
RESULTS
Pantoprazole had no impact on decrements in hearing threshold at 4-8 kHz, post-treatment elevation of urinary AKI biomarkers, or GFR (Fig. 1, Table 1). Histological response (percent necrosis) after two cycles was similar with or without pantoprazole. All eight patients with localized OS at diagnosis are alive and in remission; three of four patients with metastases at diagnosis have died.
CONCLUSION
Pantoprazole did not ameliorate cisplatin ototoxicity or nephrotoxicity. The decrease in GFR and increase in N-acetyl-ß-glucosaminidase (NAG) and creatinine demonstrate that these biomarkers can quantify cisplatin glomerular and proximal tubular toxicity. OCT2 inhibition by pantoprazole did not appear to alter antitumor response or survival.
Topics: Acute Kidney Injury; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Child, Preschool; Cisplatin; Cross-Over Studies; Doxorubicin; Female; Hearing; Hearing Loss; Humans; Kidney; Male; Methotrexate; Organic Cation Transporter 2; Osteosarcoma; Pantoprazole; Young Adult
PubMed: 29445029
DOI: 10.1634/theoncologist.2018-0037 -
Alimentary Pharmacology & Therapeutics Jan 2016Proton pump inhibitors (PPIs) have been shown to be carcinogenic in rodent studies.
BACKGROUND
Proton pump inhibitors (PPIs) have been shown to be carcinogenic in rodent studies.
AIM
As part of a long-term post-marketing surveillance study requested by the US Food and Drug Administration, to compare incidence rates of gastric and other cancers after sustained exposures to pantoprazole, a long-acting PPI, compared with other shorter acting PPIs.
METHODS
We conducted a cohort study within the membership of the Kaiser Permanente Northern California healthcare system and compared rates of gastric and other cancers among pantoprazole users and users of other PPI medications. The Cox proportional hazards model was used to adjust for potential confounders such as sex, age, receipt of treatment for Helicobacter pylori, cumulative PPI dose, total years PPI treatment and year of index date. The study was developed in consultation with, and approved by, the FDA.
RESULTS
A total of 61 684 persons with at least a 240-day supply of medication (34 178 pantoprazole and 27 686 other PPIs) were followed up for a total of 547 020 person-years (274 700 vs. 272 321 person-years, respectively). The primary analyses demonstrated comparable risks between the pantoprazole and other PPI groups for gastric cancer [hazard ratio (HR) = 0.68, 95% CI 0.24-1.93); colorectal, liver, pancreatic, or small bowel cancers (HR = 0.95, 95% CI 0.65-1.40) or any cancer (HR = 1.06, 95% CI 0.93-1.21).
CONCLUSIONS
We found no evidence that pantoprazole, a longer acting PPI, compared with shorter-acting agents, conferred an excess risk of gastric cancer, other gastrointestinal cancers or all cancers for pantoprazole compared with other shorter-acting PPIs.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; California; Cohort Studies; Dose-Response Relationship, Drug; Female; Helicobacter pylori; Humans; Male; Middle Aged; Neoplasms; Pantoprazole; Proportional Hazards Models; Proton Pump Inhibitors; Stomach Neoplasms; Time Factors; United States; Young Adult
PubMed: 26541643
DOI: 10.1111/apt.13450 -
Journal of Veterinary Internal Medicine Mar 2020Upper gastrointestinal (GI) ulceration and bleeding in critically ill dogs can cause severe anemia and increase morbidity. Acid suppressants using proton pump inhibitors...
BACKGROUND
Upper gastrointestinal (GI) ulceration and bleeding in critically ill dogs can cause severe anemia and increase morbidity. Acid suppressants using proton pump inhibitors or histamine-2 receptor blockers administered IV is commonly recommended.
HYPOTHESIS/OBJECTIVES
To evaluate the efficacy of IV administered esomeprazole, pantoprazole, and famotidine constant rate infusion (CRI) on increasing the intragastric pH of dogs. We hypothesized that esomeprazole and famotidine CRI would provide superior acid suppression compared to pantoprazole and reach pH goals for the treatment of GI bleeding.
ANIMALS
Nine healthy research Beagles.
METHODS
Randomized, 3-way crossover. Dogs received pantoprazole or esomeprazole at 1 mg/kg IV q12h and famotidine with a loading dose of 1 mg/kg followed by 8 mg/kg IV CRI daily for 3 consecutive days. The intragastric pH was recorded at baseline and for 72 hours of treatment. The mean pH and the mean percentage time (MPT) the intragastric pH was ≥3 or ≥4 were compared among and within treatment groups.
RESULTS
Significant increases in mean pH (P < 0.0001), MPT ≥3 (P < 0.001), and MPT ≥4 (P = 0.0006) were noted over time with all 3 treatments. The time effect did not differ by treatment for mean pH, MPT ≥3, and MPT ≥4 (P = .29, .56, and .37, respectively); however, only esomeprazole and famotidine CRI achieved the goals established for the treatment of gastroduodenal ulceration in people.
CONCLUSIONS AND CLINICAL IMPORTANCE
Famotidine CRI and esomeprazole might be superior acid suppressants compared to standard doses of pantoprazole for the first 72 hours of treatment.
Topics: Animals; Anti-Ulcer Agents; Cross-Over Studies; Dogs; Esomeprazole; Famotidine; Female; Hydrogen-Ion Concentration; Injections, Intravenous; Male; Pantoprazole
PubMed: 32020689
DOI: 10.1111/jvim.15718 -
Digestion 2000Proton pump inhibitors are the most effective agents for suppressing gastric acidity and are the preferred therapy for many acid-related conditions. While proton pump... (Review)
Review
Proton pump inhibitors are the most effective agents for suppressing gastric acidity and are the preferred therapy for many acid-related conditions. While proton pump inhibitors have been accessible in intravenous formulations in several European countries, they have been available only as oral drugs in the United States. In the near future, the proton pump inhibitor pantoprazole is likely to become available in an intravenous formulation for American patients. Potential uses for intravenous proton pump inhibitors include treatment of Zollinger-Ellison syndrome and peptic ulcers complicated by bleeding or gastric outlet obstruction, as well as prevention of stress ulcers and acid-induced lung injury. These intravenous proton pump inhibitors are also likely to be beneficial to patients undergoing long-term maintenance with oral proton pump inhibitors who cannot take oral therapy for a period of time. Intravenous pantoprazole is especially distinguished in its lack of clinically relevant drug interactions, and it requires no dosage adjustment for patients with renal insufficiency or with mild to moderate hepatic dysfunction. Both omeprazole and pantoprazole are well tolerated in both oral and intravenous forms. Although further studies are needed to define their roles clearly, the availability of intravenous formulations of proton pump inhibitors will certainly assist with the treatment of gastric acid-related disorders.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Gastric Acid; Gastric Acidity Determination; Gastric Outlet Obstruction; Gastrointestinal Hemorrhage; Humans; Infusions, Intravenous; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Stomach Ulcer; Sulfoxides; Zollinger-Ellison Syndrome
PubMed: 11025353
DOI: 10.1159/000007798