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Paediatric Drugs Oct 2018Pharmacokinetic data for proton pump inhibitors (PPIs), acid-suppression drugs commonly prescribed to children, are lacking for obese children who are at greatest risk...
BACKGROUND AND AIMS
Pharmacokinetic data for proton pump inhibitors (PPIs), acid-suppression drugs commonly prescribed to children, are lacking for obese children who are at greatest risk for acid-related disease. In a recent multi-center investigation, we demonstrated decreased, total body weight adjusted, apparent clearance (CL/F) of the PPI pantoprazole for obese children compared with their non-obese peers. Subsequently, we developed a population-based pharmacokinetic (PopPK) model to characterize pantoprazole disposition and evaluated appropriate pantoprazole dosing strategies for obese pediatric patients, using simulation.
METHODS
Pharmacokinetic data from the only prospective study of PPIs in obese children (aged 6-17 years; n = 40) included 273 pantoprazole and 256 pantoprazole-sulfone plasma concentrations, after single oral-dose administration, and were used for pantoprazole model development and covariate analysis (NONMEM). Model evaluation was performed via bootstrapping and predictive checks, and the final model was applied to simulate systemic pantoprazole exposures for common dosing scenarios.
RESULTS
A two-compartment PopPK model, which included CYP2C19 genotype and total body weight, provided the best fit. Resultant, typical, weight-normalized pantoprazole parameter estimates were different than previously reported for children or adults, with significantly reduced pantoprazole CL/F for obese children. Of the dosing scenarios evaluated, the weight-tiered approach, approved by the US Food and Drug Administration, achieved pantoprazole exposures [area under the curve (AUC)] within ranges previously reported as therapeutic, without over- or under-prediction for obese children.
CONCLUSIONS
Our data argue against empiric dose escalation of PPIs for obese children and support current FDA-approved pediatric weight-tiered dosing for pantoprazole; however, 3- to 5-fold inter-individual variability in pantoprazole AUC remained using this dosing approach.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adolescent; Area Under Curve; Body Weight; Child; Female; Humans; Male; Metabolic Clearance Rate; Models, Biological; Obesity; Pantoprazole; Prospective Studies; Proton Pump Inhibitors
PubMed: 30097906
DOI: 10.1007/s40272-018-0305-1 -
Iranian Journal of Pharmaceutical... 2012Stress-related mucosal damage (SRMD) is a significant cause of morbidity and mortality in critically ill patients due to the gastrointestinal blood loss. Prophylaxis of...
Stress-related mucosal damage (SRMD) is a significant cause of morbidity and mortality in critically ill patients due to the gastrointestinal blood loss. Prophylaxis of SRMD with proton pump inhibitors or histamine-2 blockers has gained widespread use in intensive care units. Both demonstrated to be effective in reducing clinically significant bleedings, while PPIs has shown to exert some anti inflammatory effects including the inhibition of producing pro-inflammatory cytokines. As cytokines have role in developing SRMD, the aim of this study was to evaluate the effect of PPIs on the inhibition of cytokine release following the critical illness. A total of 27 critically ill patients with risk factors of developing stress ulcer and intragastric pH < 3.0 enrolled to this Randomized clinical trial study. Patients were randomly assigned in three treatment groups; group one received 40 mg of intravenous pantoprazole every 12 h for 48 h (four doses), group two received 80 mg of intravenous pantoprazole every 24 h continuous infusion for 48 h and the third group received 150 mg of ranitidine intravenously as 24 h continuous infusion for 48 h. Plasma and gastric juice samples were obtained at 0th, 12th, 24th and 48th h for the measurement of EGF, IL-1β, IL-6, IL-10 and TNF-α. Pantoprazole infusion have decreased the plasma IL-1β concentrations (p = 0.041). No other significant differences in concentrations of EGF, IL-6, IL-10 and TNF-α were detected. There were reverse correlations between the intragastric pH with gastric juice IL-1β and TNF-α concentrations and a direct correlation between the intragastric pH and gastric juice EGF in pantoprazole groups. Our data suggest that pantoprazole may have some anti-inflammatory effects on patients. However, the exact impact of this effect on patients should be assessed by further studies.
PubMed: 24250536
DOI: No ID Found -
Scientific Reports Jun 2022In this work, new optical evidences concerning the changes induced of the UV light on pantoprazole sodium (PS), in solid state and as aqueous solution, are reported by...
In this work, new optical evidences concerning the changes induced of the UV light on pantoprazole sodium (PS), in solid state and as aqueous solution, are reported by UV-VIS spectroscopy, photoluminescence (PL), Raman scattering and FTIR spectroscopy. New evidences concerning the products of the PS photodegradation pathways are reported by the correlated studies of thermogravimetry and mass spectrometry. The influence of the excipients and alkaline medium on the PS photodegradation is also studied. New aspects regarding the chemical mechanism of the PS photodegradation in the presence of the water vapor and oxygen form air and the alkaline medium are shown. Our results confirm that the PS photodegradation induced of the water vapors and oxygen from air leads to the generation of 5-difluoromethoxy-3H-benzimidazole-2-thione sodium, 5-difluoromethoxy-3H-benzimidazole sodium, 2-thiol methyl-3, 4-dimethoxypyridine and 2-hydroxymethyl-3, 4-dimethoxypyridine, while in the alkaline medium, compounds of the type of the 2-oxymethyl-3,4-dimethoxypyridine sodium salts are resulted.
Topics: Benzimidazoles; Mass Spectrometry; Oxygen; Pantoprazole; Photolysis; Sodium; Spectroscopy, Fourier Transform Infrared
PubMed: 35680962
DOI: 10.1038/s41598-022-13648-6 -
Alimentary Pharmacology & Therapeutics Apr 2001
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Cyclosporine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Immunosuppressive Agents; Liver; Mixed Function Oxygenases; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Sulfoxides; Tacrolimus
PubMed: 11284790
DOI: 10.1046/j.1365-2036.2001.0877e.x -
Journal of Veterinary Internal Medicine 2015Short-term intravenous co-administration of famotidine and pantoprazole is used by some veterinarians to treat gastrointestinal bleeding in critically ill dogs. However,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Short-term intravenous co-administration of famotidine and pantoprazole is used by some veterinarians to treat gastrointestinal bleeding in critically ill dogs. However, clinical studies have not evaluated the efficacy of combination acid suppressant treatment in dogs.
HYPOTHESIS/OBJECTIVES
To compare the effect of intravenous co-administration of famotidine and pantoprazole to monotherapy with pantoprazole on intragastric pH in dogs. We hypothesized that single agent pantoprazole would be more effective than combination with famotidine.
ANIMALS
Twelve healthy adult colony dogs.
METHODS
Randomized, 2-way crossover design. All dogs received placebo (0.9% saline) for 24 hours followed by 1.0 mg/kg i.v. q12h pantoprazole or combination treatment with famotidine and pantoprazole for 3 consecutive days. Intragastric pH monitoring was used to continuously record intragastric pH for 96 hours beginning on day 0 of treatment. Mean percentage time (MPT) that intragastric pH was ≥3 and ≥4 were compared between groups using ANOVA with a posthoc Tukey-Kramer test (α = 0.017).
RESULTS
The MPT ± standard deviation intragastric pH was greater than ≥3 and 4 were 79 ± 17% and 68 ± 17% for pantoprazole and 74 ± 19% and 64 ± 23% for combination treatment, respectively. There were no significant differences in MPT intragastric pH was ≥3 and 4 between groups. Pantoprazole administered alone achieved pH goals established for humans with acid-related disorders.
CONCLUSIONS AND CLINICAL IMPORTANCE
These results suggest that short-term combination treatment with famotidine and pantoprazole is not superior to pantoprazole alone for increasing intragastric pH in dogs.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Anti-Ulcer Agents; Cross-Over Studies; Dogs; Drug Therapy, Combination; Famotidine; Female; Hydrogen-Ion Concentration; Injections, Intravenous; Male; Pantoprazole; Stomach
PubMed: 25711717
DOI: 10.1111/jvim.12555 -
Indian Journal of Critical Care... Jan 2015Stress-related mucosal disease occurs in many critically ill-patients within 24 h of admission. Proton pump inhibitor therapy has been documented to produce more potent...
BACKGROUND
Stress-related mucosal disease occurs in many critically ill-patients within 24 h of admission. Proton pump inhibitor therapy has been documented to produce more potent inhibition of gastric acid secretion than histamine 2 receptor antagonists. This study aimed to compare extemporaneous preparations of omeprazole, pantoprazole oral suspension and intravenous (IV) pantoprazole on the gastric pH in intensive care unit patients.
MATERIALS AND METHODS
This was a randomized single-blind-study. Patients of ≥ 16 years of age with a nasogastric tube, who required mechanical ventilation for ≥ 48 h, were eligible for inclusion. The excluded patients were those with active gastrointestinal bleeding, known allergy to omeprazole and pantoprazole and those intolerant to the nasogastric tube. Fifty-six patients were randomized to treatment with omeprazole suspension 2 mg/ml (40 mg every day), pantoprazole suspension 2 mg/ml (40 mg every day) and IV pantoprazole (40 mg every day) for up to 14 days. Gastric aspirates were sampled before and 1-2.5 h after the drug administration for the pH measurement using an external pH meter. Data were analyzed using SPSS (version 21.0).
RESULTS
In this study, 56 critically ill-patients (39 male, 17 female, mean age: 61.5 ± 15.65 years) were followed for the control of the gastric pH. On each of the 14 trial days the mean of the gastric pH alteration was significantly higher in omeprazole and pantoprazole suspension-treated patients than in IV pantoprazole-treated patients (P < 0.001).
CONCLUSION
Omeprazole and pantoprazole oral suspension are more effective than IV pantoprazole in increasing the gastric pH.
PubMed: 25624646
DOI: 10.4103/0972-5229.148635 -
Gastroenterology Research Oct 2017The aim of the study was to evaluate the efficacy and tolerability of fixed dose combination of amitriptyline and pantoprazole in gastroesophageal reflux disease (GERD)...
BACKGROUND
The aim of the study was to evaluate the efficacy and tolerability of fixed dose combination of amitriptyline and pantoprazole in gastroesophageal reflux disease (GERD) associated with anxiety.
METHODS
A non-randomized, open-labeled, non-comparative, multi-center study was conducted in a total of 99 patients (77 men and 22 women, mean age 44.16 ± 11.53 years). Each patient was administered a fixed dose combination of amitriptyline 10 mg and pantoprazole 40 mg once a day, for 4 weeks. GERD questionnaire, hospital anxiety and depression score (HADS) and SF-8 questionnaire (short-form health survey) were performed at baseline and at the end of study as assessment tools.
RESULTS
At the end of study, data were extractable only in 96 patients because three patients were dropped out due to loss of follow-up at week 4. GERD symptoms and anxiety score reduced significantly (P < 0.0001) at week 4 compared to baseline. SF-8 score also improved significantly (P < 0.0001) at week 4. There were no adverse events reported.
CONCLUSION
Amitriptyline and pantoprazole combination was found to be effective and safe for management in GERD patients with coexisting anxiety.
PubMed: 29118871
DOI: 10.14740/gr898e -
Alimentary Pharmacology & Therapeutics Oct 2001Several clinical trials have shown that pantoprazole (40 mg) and omeprazole (40 or 20 mg) have similar efficacy and safety in the treatment of grade II-IV reflux... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Several clinical trials have shown that pantoprazole (40 mg) and omeprazole (40 or 20 mg) have similar efficacy and safety in the treatment of grade II-IV reflux oesophagitis (Savary-Miller classification).
AIM
To compare the efficacy and safety of once-daily doses of pantoprazole (20 mg) and omeprazole (20 mg) with respect to symptom relief and healing of patients with grade I reflux oesophagitis.
METHODS
Patients with endoscopically established grade I reflux oesophagitis (non-confluent, patchy red lesions with/without white fibrin coating) were enrolled into this randomized, open, parallel-group, multicentre study. A total of 328 patients (n=166 in the pantoprazole group, n=162 in the omeprazole group) were recruited in 23 centres. Patients received 4 weeks of treatment. If the reflux oesophagitis was not completely healed, the treatment was extended to 8 weeks.
RESULTS
After 2 and 4 weeks of treatment with either pantoprazole or omeprazole, the rate of symptom relief was similar (70% vs. 79% and 77% vs. 84%, respectively). High healing rates were observed after 4 and 8 weeks (pantoprazole: 84% and 90%, respectively; omeprazole: 89% and 95%, respectively). Both treatments were well tolerated. The most frequently reported adverse events on pantoprazole and omeprazole, respectively, were nausea (8% vs. 7%), diarrhoea (5% vs. 6%) and headache (6% vs. 3%).
CONCLUSIONS
After 4 and 8 weeks of treatment with pantoprazole (20 mg) or omeprazole (20 mg), patients with mild gastro-oesophageal reflux disease (grade I) showed comparably high rates of symptom relief and healing. Both treatments were safe and well tolerated.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Benzimidazoles; Esophagitis, Peptic; Female; Humans; Male; Middle Aged; Omeprazole; Pantoprazole; Sulfoxides; Treatment Outcome
PubMed: 11563998
DOI: 10.1046/j.1365-2036.2001.01089.x -
Trials Dec 2023The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients.
OBJECTIVE
To outline the statistical analysis plan for the REVISE trial.
METHODS
REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated.
RESULTS
The primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment.
CONCLUSIONS
This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide.
TRIAL REGISTRATION
www.
CLINICALTRIALS
gov NCT03374800. November 21, 2017.
Topics: Adolescent; Humans; Critical Illness; Gastrointestinal Hemorrhage; Intensive Care Units; Pantoprazole; Pneumonia, Ventilator-Associated; Proton Pump Inhibitors; Respiration, Artificial; Adult
PubMed: 38057875
DOI: 10.1186/s13063-023-07794-z -
ISRN Pharmacology 2013The objective of this study was to investigate the bioequivalence of two formulations of 40 mg pantoprazole sodium enteric-coated tablets: Tripepsa as the test and...
The objective of this study was to investigate the bioequivalence of two formulations of 40 mg pantoprazole sodium enteric-coated tablets: Tripepsa as the test and Pantocid as the reference. The two products were administered as a single oral dose according to a randomized two-phase crossover with a 1-month washout period in 25 healthy Indian volunteers. After drug administration, serial blood samples were collected over a period of 30 hours. Plasma pantoprazole concentrations were measured by high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were analyzed based on noncompartmental analysis. The logarithmically transformed data of AUC0-∞ and Cmax were analyzed for 90% confidence intervals (CI) using ANOVA. The mean (90% CI) values for the ratio of AUC0-∞ and Cmax values of the test product over those of the reference product were 90.21 (83.69-97.24) and 108.68 (100.21-117.86), respectively (within the bioequivalence range of 80-125%). On the basis of pharmacokinetic parameters including AUC0-∞ , AUC0-t , and Cmax values, both the formulations were bioequivalent.
PubMed: 23476803
DOI: 10.1155/2013/347457