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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 -
Clinical Medicine Insights.... 2012Adding proton pump inhibitors (PPIs) to endoscopic therapy has become the mainstay of treatment for peptic ulcer bleeding, with current consensus guidelines recommending... (Review)
Review
Adding proton pump inhibitors (PPIs) to endoscopic therapy has become the mainstay of treatment for peptic ulcer bleeding, with current consensus guidelines recommending high-dose intravenous (IV) PPI therapy (IV bolus followed by continuous therapy). However, whether or not high-dose PPI therapy is more effective than low-dose PPI therapy is still debated. Furthermore, maintaining pH ≥ 4 appears to prevent mucosal bleeding in patients with acute stress ulcers; thus, stress ulcer prophylaxis with acid-suppressing therapy has been increasingly recommended in intensive care units (ICUs). This review evaluates the evidence for the efficacy of IV pantoprazole, a PPI, in preventing ulcer rebleeding after endoscopic hemostasis, and in controlling gastric pH and protecting against upper gastrointestinal (GI) bleeding in high-risk ICU patients. The review concludes that IV pantoprazole provides an effective option in the treatment of upper GI bleeding, the prevention of rebleeding, and for the prophylaxis of acute bleeding stress ulcers.
PubMed: 24833934
DOI: 10.4137/CGast.S9893 -
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 -
African Journal of Paediatric Surgery :... 2022Previous studies demonstrated faster correction of metabolic derangement associated with hypertrophic pyloric stenosis with pre-operative intravenous (IV) histamine-2...
CONTEXT
Previous studies demonstrated faster correction of metabolic derangement associated with hypertrophic pyloric stenosis with pre-operative intravenous (IV) histamine-2 receptor antagonists.
AIMS
We investigated if similar outcomes are achieved with IV pantoprazole, a proton-pump inhibitor (PPI), including the subgroup of delayed presenters in the South African setting.
SETTINGS AND DESIGN
A 5-year retrospective record review (January 2014-December 2018) compared the rate of metabolic correction in patients with hypertrophic pyloric stenosis at two tertiary centres.
SUBJECTS AND METHODS
One centre routinely administers IV pantoprazole (1 mg/kg daily) preoperatively (PPI group) and the other does not (non-PPI group). Fluid administration, chloride supplementation and post-operative emesis were evaluated.
STATISTICAL ANALYSIS
Spearman's rank correlation coefficient was used to calculate statistical significance for discrete dependent variables. Continuous variables were compared between the groups using the Student t-test. Fisher's exact contingency tables were used to classify categorical data and to assess the significance of outcome between two treatment options. P < 0.05 was considered statistically significant.
RESULTS
Forty-two patients received IV pantoprazole and 24 did not. The mean time of metabolic correction was 8 h shorter in the PPI group (P = 0.067). Total pre-operative chloride administration correlated to the rate of metabolic correction in both cohorts (P < 0.0001). Profound hypochloraemia (chloride <85 mmol/l) was corrected 23 h faster in the PPI group (P < 0.004). Post-operative emesis was noted: 0.45 episodes/patient in the PPI group and 0.75 episodes/patient in the non-PPI group (P = 0.01).
CONCLUSIONS
Pre-operative IV pantoprazole administration showed a faster correction of metabolic derangements, and in profound hypochloraemia, the correction occurred substantially faster in the PPI group. Post-operative emesis was significantly less frequent in the PPI group.
Topics: Humans; Pantoprazole; Pyloric Stenosis, Hypertrophic; Retrospective Studies
PubMed: 34916353
DOI: 10.4103/ajps.AJPS_9_21 -
Journal of Veterinary Internal Medicine 2010Despite frequent clinical use, information about the pharmacokinetics and efficacy of pantoprazole in camelids is not available.
BACKGROUND
Despite frequent clinical use, information about the pharmacokinetics and efficacy of pantoprazole in camelids is not available.
OBJECTIVES
To examine the pharmacokinetics of both IV and SC pantoprazole and to determine whether pantoprazole administration would increase 3rd compartment pH in alpacas.
ANIMALS
Six healthy adult alpacas.
METHODS
Alpacas were fitted with a 3rd compartment cannula for measuring gastric pH. After recovery, alpacas received 1 mg/kg pantoprazole IV, q24h for 3 days or 2 mg/kg SC q24h for 3 days. Alpacas received both IV and SC pantoprazole, with a minimum of 3 weeks between treatments. Third compartment pH was recorded and plasma samples were taken for pharmacokinetic analysis.
RESULTS
Pantoprazole induced a slow but sustained increase in 3rd compartment pH when given by both the IV and SC routes. Third compartment pH was significantly increased as compared with baseline values (1.81+/-0.7; mean+/-SD) at 24 (2.47+/-0.8), 48 (3.53+/-1.0) and 72 hours (4.03+/-1.3) after daily IV administration of pantoprazole. Third compartment pH increased from 1.73+/-0.6 at baseline to 3.05+/-1.1, 4.02+/-1.4, and 3.61+/-1.6 at 24, 48, and 72 hours after SC administration, respectively. Pharmacokinetic analysis demonstrated that pantoprazole had a short elimination half-life (0.47+0.06 h) and a high clearance rate (12.2+/-2.9 mL/kg/min) after both IV and SC administration.
CONCLUSIONS AND CLINICAL RELEVANCE
Based on the results of this study, pantoprazole represents a safe and effective drug for increasing 3rd compartment pH in camelids. Either IV or SC administration is likely to be an effective treatment for gastric ulcers.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Anti-Ulcer Agents; Camelids, New World; Hydrogen-Ion Concentration; Pantoprazole; Stomach Ulcer
PubMed: 20384953
DOI: 10.1111/j.1939-1676.2010.0508.x -
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 -
Clinical Pharmacology and Therapeutics Feb 2018Only limited data are available regarding the treatment of critically ill patients with clopidogrel. This trial investigated the effects and the drug concentrations of... (Clinical Trial)
Clinical Trial Comparative Study
Only limited data are available regarding the treatment of critically ill patients with clopidogrel. This trial investigated the effects and the drug concentrations of the cytochrome P450 (CYP450) activated prodrug clopidogrel (n = 43) and the half-life of the similarly metabolized pantoprazole (n = 16) in critically ill patients. ADP-induced aggregometry in whole blood classified 74% (95% confidence intervals 59-87%) of critically ill patients as poor responders (n = 43), and 65% (49-79%) responded poorly according to the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay. Although the plasma levels of clopidogrel active metabolite normally exceed the inactive prodrug ∼30-fold, the parent drug levels even exceeded those of the metabolite 2-fold in critically ill patients. The half-life of pantoprazole was several-fold longer in these patients compared with reference populations. The inverse ratio of prodrug/active metabolite indicates insufficient metabolization of clopidogrel, which is independently confirmed by the ∼5-fold increase in half-life of pantoprazole. Thus, high-risk patients may benefit from treatment with alternative platelet inhibitors.
Topics: Activation, Metabolic; Aged; Austria; Biomarkers; Blood Platelets; Cell Adhesion Molecules; Clopidogrel; Critical Illness; Cytochrome P-450 CYP2C19; Down-Regulation; Drug Monitoring; Drug Resistance; Female; Half-Life; Humans; Male; Microfilament Proteins; Middle Aged; Pantoprazole; Phosphoproteins; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Proton Pump Inhibitors
PubMed: 28913918
DOI: 10.1002/cpt.878 -
The Yale Journal of Biology and Medicine 1996Omeprazole, lansoprazole and pantoprazole are metabolized by several human cytochromes P450, most prominently by CYP2C19 and CYP3A4. Only pantoprazole is also... (Review)
Review
Omeprazole, lansoprazole and pantoprazole are metabolized by several human cytochromes P450, most prominently by CYP2C19 and CYP3A4. Only pantoprazole is also metabolized by a sulfotransferase. Differences in the quantitative contribution of these enzymes and in the relative affinities of the substrates explain some of the observed interactions with carbamazepin, diazepam, phenytoin and theophylline and of the impact of the CYP2C19 (mephenytoin) genetic polymorphism. Of these drugs, pantoprazole has the lowest potential for interactions, both in vitro and in human volunteer studies.
Topics: Animals; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Proton Pump Inhibitors; Proton Pumps
PubMed: 9165689
DOI: No ID Found -
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 -
Canadian Journal of Gastroenterology =... Apr 2009Several studies have suggested that proton pump inhibitors are efficacious in preventing rebleeding when administered immediately after endoscopic treatments. However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several studies have suggested that proton pump inhibitors are efficacious in preventing rebleeding when administered immediately after endoscopic treatments. However, there are limited clinical outcome data on the use of intravenous pantoprazole.
OBJECTIVE
To evaluate the efficacy of intravenous pantoprazole after successful endoscopic treatment for peptic ulcer bleeding using evidence from randomized controlled trials (RCTs).
METHODS
The Cochrane Library, MEDLINE, EMBASE and several Chinese databases up to July 2008 were searched. RCTs that compared the relative effectiveness of intravenous pantoprazole with placebo, H2 receptor antagonist or other agents for patients with peptic ulcer bleeding who were pretreated with successful endoscopic therapies were retrieved.
RESULTS
Five RCTs comprising a total of 821 participants were included in the final meta-analysis. Overall, there were significant differences in ulcer rebleeding (RR 0.31; 95% CI 0.18 to 0.53; pooled rates were 4.7% for pantoprazole and 15.0% for control), surgical intervention (RR 0.28, 95% CI 0.09 to 0.83; pooled rates were 1.4% in pantoprazole group versus 6.5% in control) and total length of hospital stay (weighted mean difference -1.53; 95% CI -1.91 to -1.16), but not on mortality (RR 0.72, 95% CI 0.29 to 1.81; pooled mortality rates were 1.9% for pantoprazole versus 2.8% for control) and blood transfusion requirements (weighted mean difference -0.53; 95% CI for random effects -1.04 to -0.02) when compared with control treatments. A series of subgroup analyses supported the results from the main analysis.
CONCLUSIONS
Intravenous administration of pantoprazole after endoscopic therapy for peptic ulcer bleeding reduces rates of ulcer rebleeding, surgical intervention and overall duration of hospital stay, but not mortality and blood transfusion requirements compared with placebo, H2 receptor antagonist or somatostatin.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Blood Transfusion; Chemotherapy, Adjuvant; Drug Administration Schedule; Endoscopy, Digestive System; Humans; Infusions, Intravenous; Length of Stay; Pantoprazole; Peptic Ulcer Hemorrhage; Randomized Controlled Trials as Topic; Secondary Prevention; Treatment Outcome
PubMed: 19373423
DOI: 10.1155/2009/191706