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Scientific Reports May 2022Knowing the solubility data of pharmaceutical compounds in supercritical carbon dioxide (ScCO) is essential for nanoparticles formation by using supercritical...
Knowing the solubility data of pharmaceutical compounds in supercritical carbon dioxide (ScCO) is essential for nanoparticles formation by using supercritical technology. In this work, solubility of solid pantoprazole sodium sesquihydrate in ScCO is determined and reported at 308, 318, 328 and 338 K and at pressures between 12 and 27 MPa. The solubilities are ranged between 0.0301 [Formula: see text] 10 and 0.463 [Formula: see text] 10 in mole fraction. The determined solubilities are modelled with a new model using solid-liquid equilibrium criteria and the required activity coefficient is developed using regular solution theory. The measured solubilities data are also modelled with three recent and four conventional empirical models. The recent models used are, Alwi-Garlapati (AARD = 13.1%), Sodeifian et al. (14.7%), and Tippana-Garlapati (15.5%) models and the conventional models used are Chrastil (17.54%), reformulated Chrastil (16.30%), Bartle (14.1%) and Mendenz Santiago and Teja (MT) (14.9%) models. The proposed model is correlating the data with less than 14.9% and 16.23% in terms of AARD for temperature dependent and independent cases. Among exiting models, Mendez Santiago and Teja (MT) and Alwi-Garlapati models correlate the data better than other models (corresponding AARD% and AIC are 14.9, 13.1 and -518.89, -504.14, respectively). The correlation effectiveness of the models is evaluated in terms of Corrected Akaike's Information Criterion (AIC). Finally, enthalpy of solvation and vaporization of pantoprazole sodium sesquihydrate are calculated and reported. The new model proposed in this study can be used for the combination of any complex compound with any supercritical fluid.
Topics: Carbon Dioxide; Pantoprazole; Solubility; Temperature; Thermodynamics
PubMed: 35546179
DOI: 10.1038/s41598-022-11887-1 -
Naunyn-Schmiedeberg's Archives of... Jul 2020The current study was designed to evaluate the potential abatement effect of pantoprazole against cisplatin-induced nephrotoxicity and establishing the possible...
The current study was designed to evaluate the potential abatement effect of pantoprazole against cisplatin-induced nephrotoxicity and establishing the possible protective mechanisms. Thirty-two male mice were allocated for treatment with saline, single dose of cisplatin (10 mg/kg/i.p), pantoprazole (30 mg/kg/once daily) for 5 days or combination of pantoprazole and cisplatin for 5 days. Urine, blood, and both kidneys were collected for further evaluations. Pantoprazole significantly countermand cisplatin-induced disfigurement of renal histology, kidney weight to body weight ratio, serum levels of creatinine and urea, and microalbuminuria. Furthermore, pantoprazole mostly normalized cisplatin-induced distortion of renal levels of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-10) and renal content of apoptosis regulating protein expressions (Bax, Bcl2, and active caspase 3). In addition, pantoprazole significantly subsided cisplatin-induced distortion of renal lipid peroxidation marker (MDA), renal superoxide dismutase, and catalase activities and renal reduced glutathione content. This study provides an evidence for the protective utility of short-term pantoprazole against cisplatin-induced nephrotoxicity in mice. The protective mechanism of pantoprazole could be through diminution of cisplatin-induced inflammation, oxidative stress, and their subsequent apoptotic renal cell death via abatement of apoptosis regulating protein expressions (Bax, Bcl2, and active caspase3).
Topics: Animals; Antineoplastic Agents; Apoptosis; Caspase 3; Cisplatin; Cytokines; Inflammation; Kidney Diseases; Lipid Peroxidation; Male; Mice; Oxidative Stress; Pantoprazole; Proto-Oncogene Proteins c-bcl-2; bcl-2-Associated X Protein
PubMed: 31950223
DOI: 10.1007/s00210-020-01823-3 -
International Journal of Molecular... Nov 2022Proton pump inhibitors (PPIs) are one of the most prescribed drugs around the world. PPIs induce microbiota modulation such as obesity both in humans and in animal...
Proton pump inhibitors (PPIs) are one of the most prescribed drugs around the world. PPIs induce microbiota modulation such as obesity both in humans and in animal models. However, since PPIs can induce microbiota modulation despite the absence of a high-fat diet or weight gain, it is an interesting model to correlate microbiota modulation with the establishment of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of pantoprazole treatment on TLR4 signaling and liver histology in C57BL/6J mice for 60 days, trying to correlate microbiota modulation with some aspects of liver injury. We performed glucose (GTT) and insulin (ITT) tolerance tests, serum lipopolysaccharide (LPS) dosage, liver histology, liver and intestine extraction for Western blot and qPCR. Fecal microbiota were investigated via metagenomics. Chronic treatment with pantoprazole induced microbiota modulation and impaired ileum barrier integrity, without an association with insulin resistance. Furthermore, increased circulating LPS and increased Toll-like receptor 4 (TLR4) and TGFβ downstream signaling may have an important role in the development of the observed liver microvesicular steatosis and fibrosis. Finally, this model of PPI-induced changes in microbiota might be useful to investigate liver microvesicular steatosis and fibrosis.
Topics: Mice; Humans; Animals; Toll-Like Receptor 4; Gastrointestinal Microbiome; Pantoprazole; Proton Pump Inhibitors; Lipopolysaccharides; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Fibrosis
PubMed: 36430244
DOI: 10.3390/ijms232213766 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2021The aim: Of the work was to determine the content of pro- and anti-inflammatory cytokines in the blood serum of the control group rats and after 28 days of inhibiting...
OBJECTIVE
The aim: Of the work was to determine the content of pro- and anti-inflammatory cytokines in the blood serum of the control group rats and after 28 days of inhibiting HCl secretion in the stomach by proton pump blockers "Omeprazole" and "Pantoprazole".
PATIENTS AND METHODS
Materials and methods: The studies were performed on 30 white non-linear male rats weighing 160-180 g, divided into three groups with 10 animals in each. The control (group 1) were injected intraperitoneally with water for injections within 28 days once a day. Group 2 was administered omeprazole. Group 3 was administered pantoprazole. The concentration of cytokines in the blood serum of rats was determined by the enzyme immunoassay method. For statistic data processing, Student's t-criterion for independent samples was applied.
RESULTS
Results: After prolonged administration of omeprazole and pantoprazole, the blood serum concentrations of IFNγ, TNFα, IL-1 in rats increased by 58.5% and 3.41%, 73.3% and 48.4%, 80.2% and 40.8%, respectively, and IL-12B 40p decreased by 36.6% when using omeprazole and was almost indistinguishable from the control values when pantoprazole was administered. With administration of omeprazole, IL-4 concentration decreased by 39.8% and that of pantoprazole increased by 3.86% compared to the control. Administration of omeprazole and pantoprazole did not affect IL-6 concentration.
CONCLUSION
Conclusion: Inhibition of hydrochloric acid secretion in the stomach of rats for 28 days using omeprazole and pantoprazole led to an imbalance between pro- and anti-inflammatory cytokines. The adverse effect of pantoprazole was less pronounced than that of omeprazole.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Benzimidazoles; Cytokines; Male; Proton Pump Inhibitors; Serum; Sulfoxides
PubMed: 34459754
DOI: No ID Found -
Pharmacological Research Feb 2020Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and... (Review)
Review
Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H,K-ATPase genotype. The aim of this review was to analyze the effect of genetic polymorphisms on the pharmacodynamic and pharmacokinetic properties of PPIs. The gastric acid-suppressive effect of PPIs is affected by both gastric H,K-ATPase and CYP2C19 polymorphisms, although gastric H,K-ATPase polymorphisms may have larger effects. Ilaprazole and rabeprazole show relatively small differences in the pharmacokinetic and pharmacodynamic properties and clinical efficacy among the different CYP2C19 genotypes. Compared with oral administration, the intravenous infusion of PPIs is less affected by CYP2C19 polymorphism. At the same dose, each enantiomer has less variation among different CYP2C19 genotypes than a racemate mixture.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Humans; Pharmacogenomic Variants; Proton Pump Inhibitors
PubMed: 31846760
DOI: 10.1016/j.phrs.2019.104606 -
Frontiers in Psychiatry 2023QT prolongation carries the risk of ventricular tachyarrhythmia (Torsades de Pointes) and sudden cardiac death. Psychotropic drugs can affect ventricular repolarization...
INTRODUCTION
QT prolongation carries the risk of ventricular tachyarrhythmia (Torsades de Pointes) and sudden cardiac death. Psychotropic drugs can affect ventricular repolarization and thus prolong the QT interval. The present study sought to investigate the risk factors (pharmacological and non-pharmacological) of severe QT prolongation in gerontopsychiatric patients.
METHODS
Electrocardiograms of patients on a gerontopsychiatric ward were screened for QT prolongation. Medication lists were examined utilizing the AzCERT classification. Potential drug interactions were identified with the electronic drug interaction program mediQ.
RESULTS
The overall prevalence of QT prolongation was 13.6%, with 1.9% displaying severe QT prolongation (≥ 500 ms). No statistically significant differences between patients with moderate and severe QT prolongation were identified; however, patients with severe QT prolongation tended to take more drugs ( = 0.063). 92.7% of patients with QT prolongation took at least one AzCERT-listed drug, most frequently risperidone and pantoprazole. Risperidone and pantoprazole, along with pipamperone, were also most frequently involved in potential drug interactions. All patients displayed additional risk factors for QT prolongation, particularly cardiac diseases.
CONCLUSION
In addition to the use of potentially QT-prolonging drugs, other risk factors, especially cardiac diseases, appear to be relevant for the development of QT prolongation in gerontopsychiatric patients. Pantoprazole was frequently involved in potential drug interactions and should generally not be used for more than 8 weeks in geriatric populations. As clinical consequences of QT prolongation were rare, potentially QT-prolonging drugs should not be used overcautiously; their therapeutic benefit should be considered as well. It is paramount to perform diligent benefit-risk analyses prior to the initiation of potentially QT-prolonging drugs and to closely monitor their clinical (side) effects.
PubMed: 37032947
DOI: 10.3389/fpsyt.2023.1157996 -
Advances in Therapy Aug 2020Dabigatran is a direct oral anticoagulant (DOAC) used for the treatment of several thrombotic conditions. To date, very few pharmacogenetic studies on dabigatran were... (Comparative Study)
Comparative Study
INTRODUCTION
Dabigatran is a direct oral anticoagulant (DOAC) used for the treatment of several thrombotic conditions. To date, very few pharmacogenetic studies on dabigatran were published. We aimed to investigate the influence of 59 polymorphisms in 15 genes (including CES1, UGT and CYP that encode enzymes and ABCB1 and SLC that encode transporters), concomitant treatment with pantoprazole and demographic characteristics (including sex or race) on dabigatran pharmacokinetics and safety.
METHODS
This was a candidate gene pharmacogenetic study. The study population comprised 107 volunteers enrolled in two dabigatran bioequivalence clinical trials; they were genotyped with a ThermoFisher QuantStudio 12K Flex OpenArray instrument. SPSS software v.21 was used for statistical analysis.
RESULTS
Women showed a higher exposure to dabigatran compared to men. The concomitant treatment with pantoprazole was associated with a decreased exposure to the drug. CYP2D6 poor metabolizers (PMs) were related to lower clearance (Cl/F) (p = 0.049) and a tendency was observed towards higher area under the curve (AUC), maximum concentration (C) and to lower volume of distribution (V/F) (p < 0.10). SLC22A1 haplotype was related to pharmacokinetic variability (p < 0.05). The remaining genes (including CYP, UGT1A1 and ABCB1) had no effect on dabigatran pharmacokinetics (p > 0.10). Women showed more adverse drug reactions (ADR) compared to men (0.40 ± 0.68 vs 0.15 ± 0.41 ADR per person, p = 0.03) and SLC22A1 mutant haplotype was related to a lower risk of nausea (p = 0.02).
CONCLUSION
Sex, concomitant use of pantoprazole and SLC22A1, CYP2D6 and CYP3A5 polymorphism had an effect on dabigatran pharmacokinetics and safety. Previously published pharmacogenetic predictors, namely CES1 or ABCB1 polymorphisms, had no effect on pharmacokinetics and safety. This study is of interest as it increases the scarce pharmacogenetic information on dabigatran.
Topics: ATP Binding Cassette Transporter, Subfamily B; Adolescent; Adult; Anticoagulants; Antithrombins; Area Under Curve; Carboxylic Ester Hydrolases; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Dabigatran; Female; Genotype; Humans; Male; Middle Aged; Organic Cation Transporter 1; Pantoprazole; Pharmacogenetics; Polymorphism, Genetic; Proton Pump Inhibitors; Sex Factors; Spain; Thrombosis; Young Adult
PubMed: 32564268
DOI: 10.1007/s12325-020-01414-x -
American Journal of Translational... 2021To investigate the protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats.
OBJECTIVE
To investigate the protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats.
METHODS
Healthy, specifically pathogen free SD, rats were selected and divided into 4 groups: Normal group (normal rats, without any treatment), Model group (rats received dual antiplatelet therapy: aspirin and clopidogrel), Teprenone group (rats received dual antiplatelet therapy and teprenone) and Pantoprazole group (rats received dual antiplatelet therapy and pantoprazole). The gastric mucosal blood flow, ulcer index, gastric gel mucus thickness, the levels of gastrin (Gas), prostaglandin (PG), prostaglandin E (PGE), endothelin-1 (ET-1) tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 in serum, the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and myeloperoxidase (MPO) in the gastric mucosa, as well as the expression of vascular endothelial growth factor (VEGF) in the rat's stomach were measured.
RESULTS
Compared with the Normal group, the other groups showed more severe gastric injury, elevated levels of inflammatory factors (TNF-α, IL-1β, IL-6 and IL-10), elevated levels of MDA and MPO, as well as reduced levels of GSH, SOD and VEGF (all P<0.05). Compared with the Model group, the gastric mucosal lesions in the Teprenone group and the Pantoprazole group were improved significantly (both P<0.05). Compared with the Pantoprazole group, the Teprenone group had reduced levels of ET-1 and elevated levels of PG and PGE (all P<0.05).
CONCLUSION
Teprenone protects against gastric mucosal injury induced by dual antiplatelet therapy through inhibiting gastric mucosal inflammation inhibiting oxidative stress and improving gastric mucosa indices.
PubMed: 34017431
DOI: No ID Found -
Andrology Nov 2020The effects of PPIs on human sperm fertilizing capacity were poorly investigated although these drugs are widely over-used. Two publications retrospectively studied...
BACKGROUND
The effects of PPIs on human sperm fertilizing capacity were poorly investigated although these drugs are widely over-used. Two publications retrospectively studied relationships between any PPI intake and sperm parameters from patients consulting at infertility clinics, but the conclusions of these reports were contradictory. Only two reports investigated the effects of lansoprazole and omeprazole on sperm motility and found lansoprazole to be deleterious and omeprazole to be neutral for sperm motility. The inconsistency of the PPI effect in the previous reports emphasizes the need for more basic research on human spermatozoa, taking into account the hypothesis that the different PPI drugs may have different effects on sperm physiology.
OBJECTIVES
Do PPIs, which are among the most widely sold drug in the word, impact negatively human sperm capacitation and sperm motility?
MATERIALS AND METHODS
The effects of PPIs on human sperm maturation and motility were analyzed by CASA, flow cytometry, and Western blot.
RESULTS
We tested the impact of 6 different PPIs on human sperm motility and capacitation. We showed that pantoprazole, but not the other PPIs, decreased sperm progressive motility and capacitation-induced sperm hyperactivation. We therefore investigated further the effects of pantoprazole on sperm capacitation, and we observed that it had a significant deleterious effect on the capacitation-induced hyperpolarization of the membrane potential and capacitation-associated protein phosphorylation.
DISCUSSION AND CONCLUSION
Our results indicate that exposure to pantoprazole has an adverse effect on the physiological competence of human spermatozoa. As the capacitation process takes place within the female tract, our results suggest that PPIs intake by the female partner may impair in vivo sperm maturation and possibly fertilization. Moreover, the absence of adverse effect by PPIs on mouse sperm emphasizes the need to develop reprotox assays using human material to better assess the effects of medication intake on sperm physiology.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Fertilization; Humans; Lansoprazole; Male; Membrane Potentials; Middle Aged; Omeprazole; Pantoprazole; Phosphorylation; Proton Pump Inhibitors; Rabeprazole; Retrospective Studies; Semen Analysis; Sperm Capacitation; Sperm Maturation; Sperm Motility; Spermatozoa; Young Adult
PubMed: 32609951
DOI: 10.1111/andr.12855 -
Medical Oncology (Northwood, London,... Dec 2023Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to... (Randomized Controlled Trial)
Randomized Controlled Trial
Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to cytotoxic therapy. We conducted a phase I/II randomized controlled trial in adult patients with head and neck squamous cell carcinoma (HNSCC) planned for first-line palliative chemotherapy. Patients were randomized to chemotherapy + / - intravenous (IV) pantoprazole. The primary endpoint in phase I was to determine the maximum safe dose of intravenous pantoprazole, whereas it was progression-free survival (PFS) in phase II. The dose of IV pantoprazole established in phase I was 240 mg. Between Nov'18 and Oct'20, we recruited 120 patients in phase II, 59 on pantoprazole and 61 on the standard arm. Median age was 51 years (IQR 43-60), 80% were men. Systemic therapy was IV cisplatin in 22% and oral-metronomic-chemotherapy (OMC) in 78%. Addition of pantoprazole did not prolong PFS, which was 2.2 months (95% CI 2.07-3.19) in the pantoprazole arm and 2.5 months (95% CI 2.04-3.81, HR, 1.14; 95% CI 0.78-1.66; P = 0.48) in the standard arm. Response rates were similar; pantoprazole arm 8.5%, standard arm 6.6%; P = 0.175. Overall survival was also similar; 5.6 months (95% CI 4.47-8.51) in the pantoprazole arm and 5.4 months (95% CI 3.48-8.54, HR 1.06; 95% CI 0.72-1.57; P = 0.75) in the standard arm. Grade ≥ 3 toxicities were similar. Thus, pantoprazole 240 mg IV added to systemic therapy does not improve outcomes in patients with advanced HNSCC.
Topics: Adult; Male; Humans; Middle Aged; Female; Squamous Cell Carcinoma of Head and Neck; Pantoprazole; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Tumor Microenvironment
PubMed: 38129716
DOI: 10.1007/s12032-023-02234-z