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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 -
Pharmacopsychiatry Mar 2020Polypharmacy including somatic medications such as proton pump inhibitors is a common phenomenon in psychiatric care. The aim of this study was to evaluate the...
BACKGROUND
Polypharmacy including somatic medications such as proton pump inhibitors is a common phenomenon in psychiatric care. The aim of this study was to evaluate the pantoprazole effects on clozapine metabolism.
METHODS
A large therapeutic drug-monitoring database containing plasma concentrations of CLZ was analyzed. The results were stratified into four groups: a non-smoking (n=250) and a smoking group (n=326), and two groups co-medicated with pantoprazole: non-smokers (n=26) and smokers (n=29). The analysis was based on the non-parametrical Mann-Whitney U test (M-W-U) with a significance level of 0.05.
RESULTS
Differences reached statistical significance for pharmacokinetic parameters between CLZ monotherapy and co-medication with pantoprazole neither in smokers nor in non-smokers (p>0.05 for M-W-U in pairwise comparisons). In patients with clozapine monotherapy, smokers had a higher daily dosage of CLZ compared to non-smokers (mean dosage 363±181 vs. 291±145 mg/day, p<0.001 for M-W-U).
CONCLUSIONS
Adding pantoprazole to an ongoing treatment with clozapine does not alter the metabolism of clozapine to a significant extent.
Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Databases, Factual; Drug Interactions; Drug Monitoring; Female; Humans; Male; Middle Aged; Pantoprazole; Proton Pump Inhibitors; Smokers; Young Adult
PubMed: 31614374
DOI: 10.1055/a-1021-8827 -
Cardiovascular Therapeutics Apr 2015The safety of all proton pump inhibitors (PPIs) in patients with intrinsic cardiac disease has not been well studied. In the present study, the effect of PPI... (Comparative Study)
Comparative Study
BACKGROUND
The safety of all proton pump inhibitors (PPIs) in patients with intrinsic cardiac disease has not been well studied. In the present study, the effect of PPI pantoprazole on ventricular arrhythmias induced by either ischemia or ischemia-reperfusion (I/R) was studied.
METHODS
The left main coronary artery (LAD) was ligated for 30 or 10 min followed by a 30-min reperfusion in anesthetized rats. Rats were pretreated with pantoprazole (1.3 mg/kg) or vehicle by gastric gavage (daily for 3 weeks) before ligation. Serum electrolytes levels were measured by the end of the third week before coronary ligation. Lactate dehydrogenase (LDH) activity and nitric oxide (NO) concentrations were measured at the end of the ischemia and IR injury.
RESULTS
Pantoprazole caused significant hyperkalemia by the end of third week compared with vehicle-treated rats. After LAD ligation (30 min), ventricular premature contractions (VPC), ventricular tachycardia (VT) and ventricular fibrillation (VF) were recorded in rats of the vehicle ischemia group. Pantoprazole pretreatment aggravate these arrhythmias and increased mortality. A 10-min period of ischemia followed by a 30-min reperfusion induced high incidence of VT (100%) and VF (80%) in the vehicle-treated group. The group of rats administered pantoprazole had significantly lower incidence and durations of VT and VF together with reduction of mortality rate. Pantoprazole significantly reduced serum LDH activity and NO release from myocardial tissue after both ischemia and I/R injury.
CONCLUSION
Pantoprazole aggravated ischemia-induced arrhythmias but had a significant antiarrhythmic effect on I/R-induced ventricular arrhythmias.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Disease Models, Animal; Heart Conduction System; Hyperkalemia; L-Lactate Dehydrogenase; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Nitric Oxide; Pantoprazole; Proton Pump Inhibitors; Rats, Wistar; Tachycardia, Ventricular; Time Factors; Ventricular Fibrillation; Ventricular Premature Complexes
PubMed: 25677801
DOI: 10.1111/1755-5922.12107 -
Clinical Pharmacology in Drug... Feb 2022Hydroxychloroquine as a weak basic compound with two amines is strongly enriched in cell compartments with low pH, suggesting that modification of gastric pH by... (Randomized Controlled Trial)
Randomized Controlled Trial
Hydroxychloroquine as a weak basic compound with two amines is strongly enriched in cell compartments with low pH, suggesting that modification of gastric pH by coadministered proton pump inhibitors might reduce its solubility and absorption and thus its efficacy in patients. We addressed this question in a single-center, open-label, randomized, parallel drug-drug interaction trial in healthy adults (EudraCT No. 2020-001470-30). All participants received a single oral dose of 400-mg hydroxychloroquine, and one group additionally received 40 mg of pantoprazole once daily for 9 days dosed to steady state. Whole-blood samples were collected for 72 hours, and hydroxychloroquine was quantified by liquid chromatography-tandem mass spectrometry. Primary endpoints were whole-blood hydroxychloroquine areas under the concentration-time curve from 0 to 72 hours (AUC ) and peak concentrations (C ). Unpaired 2-sided t-tests of the log transformed pharmacokinetic parameters were performed to compare both groups. Twenty-four participants (12 per group) were included. Hydroxychloroquine AUC and C did not differ between groups without and with pantoprazole (arithmetic mean; AUC , 7649 ng/ml • h, and 8429 ng/ml • h, P = .50; C , 448 ng/mL and 451.5 ng/mL, P = .96, respectively). Pantoprazole did not alter hydroxychloroquine absorption, indicating that proton pump inhibitors do not affect its bioavailability.
Topics: Adult; Biological Availability; Chromatography, Liquid; Drug Interactions; Humans; Pantoprazole; Proton Pump Inhibitors
PubMed: 34268908
DOI: 10.1002/cpdd.999 -
American Journal of Therapeutics Apr 2021
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Granuloma; Humans; Kidney; Nephritis, Interstitial; Pantoprazole
PubMed: 33852474
DOI: 10.1097/MJT.0000000000001368 -
Cellular and Molecular Neurobiology Nov 2018Gastric H/K-ATPase or vacuolar-ATPases (V-ATPases) are critical for the cancer cells survival and growth in the ischemic microenvironment by extruding protons from the...
Gastric H/K-ATPase or vacuolar-ATPases (V-ATPases) are critical for the cancer cells survival and growth in the ischemic microenvironment by extruding protons from the cell. The drugs which inhibit V-ATPases are known as proton pump inhibitors (PPIs). In the present study, we aimed to evaluate the anticancer efficacy of pantoprazole (PPZ) and its consequences on NF-κB signaling in glioma cells. We have used MTT and clonogenic assay to show PPZ effect on glioma cell growth. Propidium iodide and rhodamine 123 staining were performed to demonstrate cell cycle arrest and mitochondrial depolarization. TUNEL staining was used to evidence apoptosis after PPZ treatment. Immunoblotting and immunofluorescence microscopy were performed to depict protein levels and localization, respectively. Luciferase assay was performed to confirm NF-κB suppression by PPZ. Our results revealed PPZ treatment inhibits cell viability or growth and induced cell death in a dose- and time-dependent manner. PPZ exposure arrested G0/G1 cyclic phase and increased TUNEL positivity, caspase-3 and PARP cleavage with altered pro and anti-apoptotic proteins. PPZ also induced ROS levels and depolarized mitochondria (Δψm) with increased cytosolic cytochrome c level. Further, PPZ suppressed TNF-α stimulated NF-κB signaling by repressing p65 nuclear translocation. NF-κB luciferase reporter assays revealed significant inhibition of NF-κB gene upon PPZ treatment. PPZ exposure also reduced the expression of NF-κB-associated genes, such as cyclin-D1, iNOS, and COX-2, which indicate NF-κB inhibition. Altogether, the present study disclosed that PPZ exerts mitochondrial apoptosis and attenuates NF-κB signaling suggesting PPZ can be an effective and safe anticancer drug for glioma.
Topics: Animals; Apoptosis; Caspase 3; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Glioma; Humans; Membrane Potential, Mitochondrial; Mitochondria; NF-kappa B; Pantoprazole; Poly(ADP-ribose) Polymerases; Rats; Reactive Oxygen Species; Signal Transduction; Time Factors; Transcription Factor RelA; Tumor Necrosis Factor-alpha
PubMed: 30302629
DOI: 10.1007/s10571-018-0623-4 -
Journal of Clinical and Experimental... 2023Up-to-date data about the role of acid suppression therapy e.g. proton-pump inhibitors; to reduce post-endoscopic variceal ligation (EVL) ulcer-bleeding are...
Efficacy of Vonoprazan vs. Pantoprazole or Non-acid Suppression in Prevention of Post-variceal Ligation Ulcer Bleeding in Portal Hypertension: A Multi-arm Randomized Controlled Trial.
BACKGROUND
Up-to-date data about the role of acid suppression therapy e.g. proton-pump inhibitors; to reduce post-endoscopic variceal ligation (EVL) ulcer-bleeding are conflicting. Vonoprazan; a recently introduced potassium-competitor acid blocker, has not been studied to prevent post-EVL ulcer/bleeding. The aim was to evaluate the efficacy of vonoprazan vs. pantoprazole or non-acid suppression to prevent post-EVL ulcer/bleeding in portal hypertension patients.
MATERIAL AND METHODS
We enrolled 275 portal hypertension patients undergoing EVL in a three-arm randomized, single-blind, controlled study. A clinico-laboratory baseline evaluation was performed. Following EVL, patients were randomly and equally assigned to receive vonoprazan 20mg once daily, pantoprazole 40 mg once daily, or no acid suppression therapy. Post-EVL ulcer bleeding, ulcer dimensions, odynophagia as well as vonoprazan safety were evaluated after 2 weeks of EVL.
RESULTS
Post-EVL ulcer bleeding occurred among 2.15% of vonoprazan, 8.7% of pantoprazole, and 14.2% of the non-acid suppression groups ( < 0.001). Post-ligation ulcer frequency and dimensions were higher among non-acid suppression and pantoprazole groups vs. vonoprazan ( < 0.05). Chest pain and odynophagia were encountered among 73.6% and 54.9% of the non-acid suppression group vs. 39.6% and 45.1% in pantoprazole, and 17.2% and 21.5% in vonoprazan groups, respectively ( < 0.05). There were no vonoprazan-related adverse events. Non-use of vonoprazan was the strongest independent predictor for post-EVL bleeding.
CONCLUSION
Short course of vonoprazan 20 mg/day is safe and superior to pantoprazole 40 mg/day in the reduction of post-EVL ulcer dimensions at 2 weeks post-EVL, and prevention of ulcer-related bleeding. Acid suppression is superior to no acid suppression to prevent post-EVL complications.
PubMed: 37975046
DOI: 10.1016/j.jceh.2023.05.008 -
Intensive Care Medicine Apr 2020
Topics: Adult; Histamine H2 Antagonists; Humans; Intensive Care Units; Pantoprazole; Peptic Ulcer; Ulcer
PubMed: 32076767
DOI: 10.1007/s00134-020-05959-x -
Journal of Natural Medicines Jan 2016The present study was designed to elucidate the mechanism(s) of the gastro-protective effect of crocin against indomethacin-induced gastric lesions. Crocin or...
The present study was designed to elucidate the mechanism(s) of the gastro-protective effect of crocin against indomethacin-induced gastric lesions. Crocin or pantoprazole was administered to rats 30 min before indomethacin. Five hours later, the animals were killed and their stomachs were removed and examined macroscopically. Samples of gastric mucosa were collected for microscopic evaluation, mRNA expression of caspase-3, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 was quantified by RT-PCR, and protein levels of COX-1, COX-2, iNOS and caspase-3 were assessed by Western blotting. The pH, volume of gastric effluent and antioxidant activity were measured in 5 separate groups of rats following pylorus ligation. Indomethacin induced significant increases in mRNA and protein expression of iNOS and caspase-3 and increased MDA levels, and reduced the pH of the gastric effluent and protein and mRNA expression of COX-2 and protein expression of COX-1 and mucus content associated with gastric ulceration. Crocin and pantoprazole significantly inhibited mRNA and protein expression of iNOS, caspase-3 and MDA, and reduced mucus content induced by indomethacin. However, unlike pantoprazole, crocin failed to increase COX-1 and pH, but had variable increasing effects on mRNA and protein expression of COX-2. Macroscopic and microscopic observations showed that mucosal erosions induced by indomethacin were significantly inhibited by pantoprazole and crocin. These findings suggest that crocin exerts its gastro-protective effects mainly by inhibition of MDA, reduction in iNOS and caspase-3, and inhibition of the reduction in mucus content induced by indomethacin. Crocin is a novel agent that has potential in the prevention of ulceration induced by NSAIDs.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carotenoids; Caspase 3; Cyclooxygenase 1; Cyclooxygenase 2; Gastric Mucosa; Indomethacin; Male; Membrane Proteins; Nitric Oxide Synthase Type II; Pantoprazole; RNA, Messenger; Rats; Rats, Wistar; Stomach Ulcer
PubMed: 26439477
DOI: 10.1007/s11418-015-0938-0 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2021The aim: Was to characterize the morphological peculiarities of the gastric mucosa at early stage of prescription of acetylsalicylic acid (ASA) and clopidogrel as well...
OBJECTIVE
The aim: Was to characterize the morphological peculiarities of the gastric mucosa at early stage of prescription of acetylsalicylic acid (ASA) and clopidogrel as well as to study the impact of pantoprazole on the gastric mucosa to optimize the prophylaxis and treatment of gastropathies induced by ASA and clopidogrel.
PATIENTS AND METHODS
Materials and methods: The experiments were performed on 77 non-linear white male rats with the average weight of 150-180 g. Depending on the aim of research, the animals were divided into 7 groups.
RESULTS
Results: The administration of pantoprazole in combination with ASA and clopidogrel presented positive trends in neutral glycoproteins amount and contributes to preventing GM necrotic lesions by amplification of protective properties of mucus and stabilization of apoptotic activity of gastric epithelial cells.
CONCLUSION
Conclusions: 1. According to our study findings, administration of ASA in combination with clopidogrel results in 2,5 times higher risk of GM erosive lesions. 2. One of the most significant morphological manifestations of gastropathy in ASA and clopidogrel regimen is the development of microerosions, which are poorly diagnosed by macroscopic examination. 3. The use of PAS-reaction makes possible to identify damage to the basal membrane of superficial epitheliocytes, which may be a top-priority morphological criterion of gastropathy induced by ASA or clopidogrel in the absence of an inflammatory reaction. 4. Administration of pantoprazole in combination with ASA and clopidogrel contributes to preventing GM necrotic lesions by amplification of protective properties of mucus and stabilization of apoptotic activity of gastric epithelial cells.
Topics: Animals; Aspirin; Clopidogrel; Gastric Mucosa; Male; Pantoprazole; Rats; Ticlopidine
PubMed: 33813477
DOI: No ID Found