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The New England Journal of Medicine Dec 2018Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear.
METHODS
In this European, multicenter, parallel-group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization.
RESULTS
A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups.
CONCLUSIONS
Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo. (Funded by Innovation Fund Denmark and others; SUP-ICU ClinicalTrials.gov number, NCT02467621 .).
Topics: Aged; Critical Illness; Female; Gastrointestinal Hemorrhage; Humans; Injections, Intravenous; Intensive Care Units; Male; Middle Aged; Pantoprazole; Peptic Ulcer; Proton Pump Inhibitors; Risk Factors; Single-Blind Method; Stress, Physiological; Survival Analysis
PubMed: 30354950
DOI: 10.1056/NEJMoa1714919 -
BMC Pharmacology & Toxicology Jul 2020The pharmacokinetics of proton pump inhibitors (PPIs) may be affected by food intake. We aimed to evaluate the effect of food on the pharmacokinetics of omeprazole,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The pharmacokinetics of proton pump inhibitors (PPIs) may be affected by food intake. We aimed to evaluate the effect of food on the pharmacokinetics of omeprazole, rabeprazole, and pantoprazole.
SETTING
The study population comprised 186 healthy volunteers participating in 6 bioequivalence clinical trials.
METHOD
Subjects were evaluated to determine the effect of a high-fat breakfast on the pharmacokinetics of omeprazole (n = 36), rabeprazole (n = 69), and pantoprazole (n = 81).
MAIN OUTCOME MEASURE
Drug plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry.
RESULTS
Food affected the pharmacokinetics of omeprazole (increased T and decreased AUC and C), pantoprazole (increased T and decreased AUC), and rabeprazole (increased T, C and half-life). Food increased variability in T for all 3 drugs, delaying absorption around 3 to 4 h and until 20 h in some subjects.
CONCLUSION
As food delays the absorption of PPIs and increases their variability, it would be better to administer these drugs under fasting conditions.
TRIAL REGISTRATION
European Union Drug Regulating Authorities Clinical Trials Database: EudraCT : 2004-003863-59 (registration date 05/MAR/2004), EudraCT 2006-001162-17 (registration date 17-MAR-2006), EudraCT: 2007-002489-37 (registration date 12-JUN-2007), EudraCT: 2007-002490-31 (registration date 12-JUN-2007), EudraCT: 2010-024029-19 (registration date 23-NOV-2010).
Topics: Adult; Anti-Ulcer Agents; Cross-Over Studies; Cytochrome P-450 CYP2C19; Dietary Fats; Fasting; Female; Food-Drug Interactions; Genotype; Humans; Male; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Young Adult
PubMed: 32711578
DOI: 10.1186/s40360-020-00433-2 -
Postgraduate Medical Journal Jan 2022
Topics: Carcinoma, Hepatocellular; Hepatitis; Humans; Liver Neoplasms; Pantoprazole
PubMed: 33273111
DOI: 10.1136/postgradmedj-2020-138838 -
The New England Journal of Medicine Mar 2019
Topics: Gastrointestinal Hemorrhage; Humans; Intensive Care Units; Pantoprazole; Proton Pump Inhibitors
PubMed: 30855751
DOI: 10.1056/NEJMc1900206 -
The New England Journal of Medicine Mar 2019
Topics: Gastrointestinal Hemorrhage; Humans; Intensive Care Units; Pantoprazole; Proton Pump Inhibitors
PubMed: 30855750
DOI: 10.1056/NEJMc1900206 -
European Journal of Gastroenterology &... Jan 2004To perform a systematic review on the efficacy of pantoprazole based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy... (Meta-Analysis)
Meta-Analysis Review
AIM
To perform a systematic review on the efficacy of pantoprazole based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of pantoprazole and other proton pump inhibitors (PPIs) when co-prescribed with antibiotics.
METHODS
Studies evaluating pantoprazole combined with antibiotics were considered. Only randomized clinical trials comparing pantoprazole and other PPIs when co-prescribed with antibiotics, and differing only in the PPI (pantoprazole vs other), were eligible for inclusion in the meta-analysis. Bibliographical searches in several electronic databases, and manual search of abstracts from congresses, were conducted. The percentage (weighted mean) of patients with eradication success was calculated. Meta-analysis was performed combining the odds ratios (ORs) of the individual studies in a global OR.
RESULTS
The mean eradication rate with pantoprazole plus clarithromycin for 14 days was 60%. Cure rates with 7 day pantoprazole based triple regimens were higher: pantoprazole, amoxicillin and clarithromycin (78%); pantoprazole, clarithromycin and nitroimidazole (84%); and pantoprazole, amoxicillin and nitroimidazole (74%). Twelve studies comparing pantoprazole and other PPIs were selected for the meta-analysis, including 534 and 603 patients, respectively. The mean eradication rate for H. pylori using pantoprazole plus antibiotics was 83%, and 81% when other PPIs were used (OR = 1; 95% confidence interval (CI) from 0.61 to 1.64). When sub-analysis was performed, including only studies comparing pantoprazole with omeprazole, or pantoprazole with lansoprazole, differences were also statistically non-significant. The meta-analysis of the six studies prescribing equivalent doses of all PPIs demonstrated similar results with pantoprazole and with other PPIs (OR = 1.07; 95% CI from 0.71 to 1.62), the results being statistically homogeneous.
CONCLUSIONS
Pantoprazole achieves similar cure rates to those of omeprazole and lansoprazole when co-prescribed with antibiotics for the eradication of H. pylori infection.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Infective Agents; Benzimidazoles; Drug Therapy, Combination; Enzyme Inhibitors; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Sulfoxides
PubMed: 15095858
DOI: 10.1097/00042737-200401000-00014 -
Expert Opinion on Drug Metabolism &... Apr 2008Conditions requiring inhibition of acid secretion, such as gastro-oesophageal reflux disease (GORD), peptic ulcers, non-ulcer dyspepsia or the use of NSAIDs, are very... (Review)
Review
BACKGROUND
Conditions requiring inhibition of acid secretion, such as gastro-oesophageal reflux disease (GORD), peptic ulcers, non-ulcer dyspepsia or the use of NSAIDs, are very common, and their prevalence is expecting to rise as they are seen predominantly amongst the elderly. Among the drugs available to inhibit acid secretion, proton pump inhibitors (PPI) have been shown to have the best efficacy-safety ratio and have been used widely.
OBJECTIVE
This paper was intended to provide an overall presentation of one of these PPIs, pantoprazole.
METHOD
This study was first intended to give an overview of pantoprazole, so a Medline search was conducted using pantoprazole as unique search term, without publication date restriction. We found 826 references for pantoprazole and selected some of the most relevant publications to conduct this review.
RESULTS/CONCLUSION
Five different PPIs are commercially available: omeprazole, pantoprazole, rabeprazole, lansoprazole and esomeprazole. Pantoprazole differs from other PPIs by a selective binding to the ion transport pathway, a good stability at neutral pH values, and a relatively robust plasma concentration-time curve. These pharmacokinetic differences may not be fully converted into pharmacodynamic differences of pantoprazole versus other PPIs. Pantoprazole has been assessed in most of the clinical situations where acid suppression is required, and showed great efficacy and an excellent safety profile. Some safety concerns were raised with long-term use of PPIs, but they are well balanced by the benefit of PPIs for patients with conditions such as GORD or peptic ulcer.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Clinical Trials as Topic; Gastroesophageal Reflux; Humans; Pantoprazole; Peptic Ulcer; Proton Pump Inhibitors; Treatment Outcome
PubMed: 18433349
DOI: 10.1517/17425255.4.4.471 -
Hospital Medicine (London, England :... Jul 1999Pantoprazole is a proton pump inhibitor which has recently had its clinical license extended to include maintenance therapy for the treatment of reflux oesophagitis,... (Review)
Review
Pantoprazole is a proton pump inhibitor which has recently had its clinical license extended to include maintenance therapy for the treatment of reflux oesophagitis, Helicobacter pylori eradication and short-term intravenous administration. This article reviews the history of gastric acid secretion and examines the role of proton pump inhibitors, particularly pantoprazole, in the treatment of acid-related disorders.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Drug Interactions; Female; Gastric Acid; Gastric Juice; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Omeprazole; Pantoprazole; Peptic Ulcer; Pregnancy; Proton Pump Inhibitors; Sulfoxides; Treatment Outcome
PubMed: 10605542
DOI: 10.12968/hosp.1999.60.7.1743 -
Digestive Diseases and Sciences Mar 2024Low-dose aspirin (LDA) administration is associated with an elevated risk of recurring peptic ulcer (PU) and gastrointestinal (GI) hemorrhage. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Low-dose aspirin (LDA) administration is associated with an elevated risk of recurring peptic ulcer (PU) and gastrointestinal (GI) hemorrhage.
AIMS
This systematic review and Bayesian network meta-analysis aimed to comprehensively assess the effectiveness of diverse medications in preventing the recurrence of PU and GI hemorrhage in patients with a history of PU receiving long-term LDA therapy.
METHODS
This systematic review and network meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered on PROSPERO (CRD42023406550). We searched relevant studies in main databases from inception to March 2023. All statistical analyses were performed using R (version 4.1.3), with the "Gemtc" (version 1.0-1) package. The pooled risk ratio (RR), corresponding 95% credible interval (95% CrI), and the surface under the cumulative ranking curve (SUCRA) were calculated.
RESULTS
11 Randomized clinical trials (RCTs) were included. The analysis underscored pantoprazole was the most efficacious for reducing the risk of PU recurrence (RR [95% CrI] = 0.02 [0, 0.28]; SUCRA: 90.76%), followed by vonoprazan (RR [95% CrI] = 0.03 [0, 0.19]; SUCRA: 86.47%), comparing with the placebo group. Pantoprazole also performed well in preventing GI hemorrhage (RR [95% CrI] = 0.01[0, 0.42]; SUCRA: 87.12%) compared with Teprenone.
CONCLUSIONS
For patients with a history of PU receiving LDA, pantoprazole and vonoprazan might be the optimal choices to prevent PU recurrence and GI hemorrhage.
Topics: Humans; Pantoprazole; Peptic Ulcer; Aspirin; Gastrointestinal Hemorrhage; Pyrroles; Sulfonamides
PubMed: 38252210
DOI: 10.1007/s10620-023-08233-4 -
Scientific Reports Dec 2020Proton pump inhibitors (PPIs) belong to the most common medication in geriatric medicine. They are known to reduce osteoclast activity and to delay fracture healing in...
Proton pump inhibitors (PPIs) belong to the most common medication in geriatric medicine. They are known to reduce osteoclast activity and to delay fracture healing in young adult mice. Because differentiation and proliferation in fracture healing as well as pharmacologic actions of drugs markedly differ in the elderly compared to the young, we herein studied the effect of the PPI pantoprazole on bone healing in aged mice using a murine fracture model. Bone healing was analyzed by biomechanical, histomorphometric, radiological and protein biochemical analyses. The biomechanical analysis revealed a significantly reduced bending stiffness in pantoprazole-treated animals when compared to controls. This was associated with a decreased amount of bone tissue within the callus, a reduced trabecular thickness and a higher amount of fibrous tissue. Furthermore, the number of osteoclasts in pantoprazole-treated animals was significantly increased at 2 weeks and decreased at 5 weeks after fracture, indicating an acceleration of bone turnover. Western blot analysis showed a lower expression of the bone morphogenetic protein-4 (BMP-4), whereas the expression of the pro-angiogenic parameters was higher when compared to controls. Thus, pantoprazole impairs fracture healing in aged mice by affecting angiogenic and osteogenic growth factor expression, osteoclast activity and bone formation.
Topics: Aging; Animals; Bone Morphogenetic Protein 4; Disease Models, Animal; Fracture Healing; Mice; Neovascularization, Physiologic; Osteogenesis; Pantoprazole
PubMed: 33361800
DOI: 10.1038/s41598-020-79605-3