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Frontiers in Pharmacology 2024The development of resistance to carbapenems in due to the production of metallo-β-lactamases (MBLs) is a critical public health problem because carbapenems are the...
The development of resistance to carbapenems in due to the production of metallo-β-lactamases (MBLs) is a critical public health problem because carbapenems are the last-resort drugs used for treating severe infections of extended-spectrum β-lactamases (ESBLs) producing . Restoring the activity of carbapenems by the inhibition of metallo-β-lactamases is a valuable approach to combat carbapenem resistance. In this study, two well-characterized clinical multidrug and carbapenem-resistant isolates were used. The sub-inhibitory concentrations of pantoprazole and the well-reported metallo-β-lactamase inhibitor captopril inhibited the hydrolytic activities of metallo-β-lactamases, with pantoprazole having more inhibiting activities. Both drugs, when used in combination with meropenem, exhibited synergistic activities. Pantoprazole could also downregulate the expression of the metallo-β-lactamase genes and . A docking study revealed that pantoprazole could bind to and chelate zinc ions of New Delhi and Verona integron-encoded MBL (VIM) enzymes with higher affinity than the control drug captopril and with comparable affinity to the natural ligand meropenem, indicating the significant inhibitory activity of pantoprazole against metallo-β-lactamases. In conclusion, pantoprazole can be used in combination with meropenem as a new strategy for treating serious infections caused by metallo-β-lactamases producing .
PubMed: 38533260
DOI: 10.3389/fphar.2024.1366459 -
CPT: Pharmacometrics & Systems... Jun 2024Pantoprazole is a proton pump inhibitor indicated for the treatment of gastroesophageal reflux disease, a condition that disproportionately affects children with...
Pantoprazole is a proton pump inhibitor indicated for the treatment of gastroesophageal reflux disease, a condition that disproportionately affects children with obesity. Appropriately dosing pantoprazole in children with obesity requires understanding the body size metric that best guides dosing, but pharmacokinetic (PK) trials using traditional techniques are limited by the need for larger sample sizes and frequent blood sampling. Physiologically-based PK (PBPK) models are an attractive alternative that can account for physiologic-, genetic-, and drug-specific changes without the need for extensive clinical trial data. In this study, we explored the effect of obesity on pantoprazole PK and evaluated label-suggested dosing in this population. An adult PBPK model for pantoprazole was developed using data from the literature and accounting for genetic variation in CYP2C19. The adult PBPK model was scaled to children without obesity using age-associated changes in anatomical and physiological parameters. Lastly, the pediatric PBPK model was expanded to children with obesity. Three pantoprazole dosing strategies were evaluated: 1 mg/kg total body weight, 1.2 mg/kg lean body weight, and US Food and Drug Administration-recommended weight-tiered dosing. Simulated concentration-time profiles from our model were compared with data from a prospective cohort study (PAN01; NCT02186652). Weight-tiered dosing resulted in the most (>90%) children with pantoprazole exposures in the reference range, regardless of obesity status or CYP2C19 phenotype, confirming results from previously published population PK models. PBPK models may allow for the efficient study of physiologic and developmental effects of obesity on PK in special populations where clinical trial data may be limited.
PubMed: 38837864
DOI: 10.1002/psp4.13167 -
Journal of Chromatographic Science May 2024This technique is employed for the simultaneous quantification of aspirin (ASP) and pantoprazole sodium in both pure powder form and formulations. The high performance...
This technique is employed for the simultaneous quantification of aspirin (ASP) and pantoprazole sodium in both pure powder form and formulations. The high performance liquid chromatography (HPLC) method uses a C-18 column (250 mm × 4.6 mm, 5 μm) with a mobile phase consisting of 0.05 M disodium hydrogen phosphate and methanol in a 40:60% v/v ratio. The flow rate is maintained at 1.0 mL/min. On a layer of silica gel 60F254 with an aluminum backing, the high performance thin layer chromatography (HPTLC) separation was carried out with ethyl acetate and methanol (8: 1.5 v/v) as the mobile phase. With a mean recovery of 100.54% and 99.55% for ASP and PNT, respectively, quantification was accomplished using the HPLC method with UV detection at 286 nm over the concentration range of 0.1-0.6 g/mL for PNT and 0.4-2.4 g/mL for ASP. With a mean recovery of 99.44% and 99.01% for ASP and PNT, respectively, quantification was achieved using the HPTLC method with UV detection at 298 nm over the concentration range of 400-2400 ng/spot for ASP and 100-600 ng/spot for PNT, respectively. The methods can be used for the simultaneous determination of ASP and PNT in pure powder form and formulations as they are simple, accurate and sensitive.
Topics: Pantoprazole; Aspirin; Chromatography, High Pressure Liquid; Reproducibility of Results; Linear Models; Chromatography, Thin Layer; Limit of Detection; 2-Pyridinylmethylsulfinylbenzimidazoles; Tablets
PubMed: 38553784
DOI: 10.1093/chromsci/bmae012 -
Cureus Oct 2023Current practice for patients with suspected or confirmed upper gastrointestinal bleeding (GIB) is to utilize a proton pump inhibitor (PPI) bolus followed by a...
Comparison Between Pantoprazole Intermittent Dosing and Continuous Infusion in Suspected Upper Gastrointestinal Bleeding Prior to Endoscopy: Impact of a Pharmacist-Driven Protocol to Reduce Utilization of Pantoprazole Continuous Infusion.
BACKGROUND
Current practice for patients with suspected or confirmed upper gastrointestinal bleeding (GIB) is to utilize a proton pump inhibitor (PPI) bolus followed by a continuous infusion for 72 hours. Literature has shown similar outcomes with intermittent bolus dosing compared to continuous infusion. Substitution would lead to reduced costs and utilization of resources.
METHODS
This was a retrospective case-control study conducted via chart review. Utilizing electronic healthcare record reports, patients in the control arm were screened for inclusion if they received a pantoprazole continuous infusion from December 1, 2020, to March 31, 2021. A total of 38 patients were included in the control arm. Patients in the experimental arm were screened for inclusion with pantoprazole intermittent therapy from January 1, 2022, to June 30, 2022. A total of 60 patients were included in the experimental arm. The primary outcome was a 30-day GIB recurrence. Secondary outcomes included 30-day hospital readmission, 30-day (), hospital length of stay (LOS), and number of pantoprazole vials utilized.
RESULTS
There was a 65% reduction in the 30-day GIB recurrence in the intermittent bolus arm compared to the continuous infusion arm. Thirty-day hospital readmission was 57% lower in the intermittent bolus arm compared to the continuous infusion arm. The LOS between the two arms was almost identical with the median being five days for the intermittent bolus arm and the median being four days for the continuous infusion arm. The 30-day infection rate had 5% of patients acquiring in the intermittent bolus arm and 2.5% in the continuous infusion arm. The intermittent bolus arm used 55% fewer pantoprazole vials than the continuous infusion arm.
CONCLUSION
In hospitalized patients, the utilization of pantoprazole intermittent bolus is not only comparably efficacious but potentially represents a safer and economically advantageous alternative compared to the current guideline recommendation of a 72-hour pantoprazole continuous infusion. Further studies could provide more robust data to support our findings and challenge the current recommendation for patients who meet the indication criteria.
PubMed: 38046478
DOI: 10.7759/cureus.48056 -
Medical Oncology (Northwood, London,... Jun 2024FOXM1, a proto-oncogenic transcription factor, plays a critical role in cancer development and treatment resistance in cancers, particularly in breast cancer. Thus, this...
FOXM1, a proto-oncogenic transcription factor, plays a critical role in cancer development and treatment resistance in cancers, particularly in breast cancer. Thus, this study aimed to identify potential FOXM1 inhibitors through computational screening of drug databases, followed by in vitro validation of their inhibitory activity against breast cancer cells. In silico studies involved pharmacophore modeling using the FOXM1 inhibitor, FDI-6, followed by virtual screening of DrugBank and Selleckchem databases. The selected drugs were prepared for molecular docking, and the crystal structure of FOXM1 was pre-processed for docking simulations. In vitro studies included MTT assays to assess cytotoxicity, and Western blot analysis to evaluate protein expression levels. Our study identified Pantoprazole and Rabeprazole as potential FOXM1 inhibitors through in silico screening and molecular docking. Molecular dynamics simulations confirmed stable interactions of these drugs with FOXM1. In vitro experiments showed both Pantoprazole and Rabeprazole exhibited strong FOXM1 inhibition at effective concentrations and that showed inhibition of cell proliferation. Rabeprazole showed the inhibitor activity at 10 µM in BT-20 and MCF-7 cell lines. Pantoprazole exhibited FOXM1 inhibition at 30 µM and in BT-20 cells and at 70 µM in MCF-7 cells, respectively. Our current study provides the first evidence that Rabeprazole and Pantoprazole can bind to FOXM1 and inhibit its activity and downstream signaling, including eEF2K and pEF2, in breast cancer cells. These findings indicate that rabeprazole and pantoprazole inhibit FOXM1 and breast cancer cell proliferation, and they can be used for FOXM1-targeted therapy in breast or other cancers driven by FOXM1.
Topics: Humans; Forkhead Box Protein M1; Drug Repositioning; Breast Neoplasms; Molecular Docking Simulation; Female; Rabeprazole; MCF-7 Cells; Cell Proliferation; Molecular Dynamics Simulation; Antineoplastic Agents; Pantoprazole; Cell Line, Tumor; Pyridines; Thiophenes
PubMed: 38918225
DOI: 10.1007/s12032-024-02427-0 -
Scientific Reports Jan 2024Most proton pump inhibitors (PPIs) inhibit the bioactivation of clopidogrel to its active metabolite. There is controversy concerning whether PPIs alter the...
Most proton pump inhibitors (PPIs) inhibit the bioactivation of clopidogrel to its active metabolite. There is controversy concerning whether PPIs alter the effectiveness of clopidogrel in reducing the risk of ischemic stroke (IS). We therefore aimed to examine the risk of IS associated with concomitant use of clopidogrel and omeprazole, a PPI commonly used in clinical settings. We conducted a retrospective cohort study using the National Health Insurance Research Database of Taiwan dated from 2000 to 2013. The study cohorts comprised 407 patients diagnosed with acute coronary syndrome (ACS) and with concomitant use of clopidogrel and omeprazole (the exposed cohort), 814 ACS patients with single use of clopidogrel (the comparison cohort), and 230 ACS patients with concurrent use of clopidogrel and pantoprazole (the reference cohort). The primary outcome was incident IS. The hazard ratios (HRs) and 95% confidence intervals (CIs) derived from the time-dependent Cox regression model were used to assess the association between concomitant use of clopidogrel and omeprazole and the risk of IS. The incidence rate of IS was significantly higher in the exposed cohort (81.67 per 1000 person-years) than in the comparison cohort (57.45 per 1000 person-years), resulting in an adjusted HR of 1.39 (95% CI 1.03-1.74). By contrast, there was no significant difference in the risk of IS between the exposed and reference cohorts (adjusted HR 1.11; 95% CI 0.81-1.52). The present study revealed that patients taking both clopidogrel and omeprazole was associated with an increased risk of IS.
Topics: Humans; Clopidogrel; Proton Pump Inhibitors; Cohort Studies; Omeprazole; Platelet Aggregation Inhibitors; Ticlopidine; Retrospective Studies; Ischemic Stroke; Acute Coronary Syndrome; Drug Interactions
PubMed: 38242975
DOI: 10.1038/s41598-024-51682-8 -
Analytical Methods : Advancing Methods... May 2024This study introduces a novel approach for the simultaneous determination of topotecan (TOP) and pantoprazole (PNT), two drugs whose interaction is critical in clinical...
This study introduces a novel approach for the simultaneous determination of topotecan (TOP) and pantoprazole (PNT), two drugs whose interaction is critical in clinical applications. The significance of this study originates from the need to understand the pharmacokinetic changes of TOP after PNT administration, which can inform necessary dose adjustments of TOP. To achieve this, nitrogen blue emissive carbon dots (B@NCDs) were produced and employed due to their unique fluorescent properties. When TOP is added to B@NCDs, it exhibits strong native fluorescence at 545 nm without influencing the B@NCDs' fluorescence at 447 nm. Conversely, PNT causes quenching of B@NCDs fluorescence, a property that enables the distinct detection of both drugs. The B@NCDs were fully characterized using different techniques, including ultraviolet-visible spectrophotometry, fluorescence analysis, X-ray diffraction (XRD), transmission electron microscopy (TEM), and FTIR spectroscopy. The proposed method demonstrated excellent linearity, selectivity, and sensitivity, with low detection limits (LOD, S/N = 3); 0.0016 μg mL for TOP and 0.36 μg mL for PNT. Applied to spiked rabbit plasma samples, this method offers a new approach for evaluating the pharmacokinetic interaction between TOP and PNT. It enables the determination of all pharmacokinetic parameters of TOP before and after coadministration with PNT, providing essential insights into whether dose adjustments are necessary. This research not only contributes to the field of drug monitoring and interaction studies but also exemplifies the potential of B@NCDs in complex biological matrices, paving the way for further pharmacological and therapeutic applications.
Topics: Pantoprazole; Topotecan; Carbon; Quantum Dots; Spectrometry, Fluorescence; Animals; Limit of Detection; Fluorescent Dyes
PubMed: 38738631
DOI: 10.1039/d4ay00394b -
Cell Biochemistry and Function Mar 2024A drug interaction is a condition in which two or more drugs are taken at the same time. Type 2 diabetes mellitus is a significant contributor to polypharmacy. Proton... (Review)
Review
A drug interaction is a condition in which two or more drugs are taken at the same time. Type 2 diabetes mellitus is a significant contributor to polypharmacy. Proton pump inhibitors (PPIs) are often prescribed in combination with metformin or DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin) or a combined dose of metformin and DPP-4 inhibitor to treat gastritis in diabetic patients. This review article mainly focused on evaluating the potential drug-drug interactions (DDIs) between PPIs (i.e. esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) with metformin and PPIs with DPP-4 inhibitors. The findings demonstrated the existence of pharmacokinetic and pharmacodynamic DDIs between the aforementioned PPIs with metformin and DPP-4 inhibitors, which could impact the biological activities (i.e., hypoglycemia) of these drugs. Moreover, this review suggested that esomeprazole could be the best drug in the PPI group to be prescribed simultaneously with metformin and DPP-4 inhibitors, as most of the antidiabetic drugs of this study did not show any interaction with esomeprazole. The findings of this study also revealed that both antidiabetic drugs and PPIs could have positive interactions as PPIs have the potential to lessen the gastrointestinal side effects of metformin and DPP-4 inhibitors. To achieve the greatest therapeutic impact with the fewest side effects, careful dose control of these drugs is required. So, more extensive research on both human and animal subjects are needed to ascertain the veracity of this hypothesis.
Topics: Animals; Humans; Proton Pump Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Esomeprazole; Metformin; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Drug Interactions
PubMed: 38480622
DOI: 10.1002/cbf.3967 -
Frontiers in Cellular and Infection... 2024Azole resistance has been increasingly reported and become an issue for clinical managements of invasive mycoses. New strategy with combination therapy arises as a...
INTRODUCTION
Azole resistance has been increasingly reported and become an issue for clinical managements of invasive mycoses. New strategy with combination therapy arises as a valuable and promising alternative option. The aim of the present study is to investigate the combinational effect of proton pump inhibitors (PPIs) and azoles against pathogenic fungi.
METHODS
interactions of PPIs including omeprazole (OME), lansoprazole (LAN), pantoprazole (PAN), and rabeprazole (RAB), and commonly used azoles including itraconazole (ITC), posaconazole (POS), voriconazole (VRC) and fluconazole (FLC), were investigated via broth microdilution chequerboard procedure adapted from the CLSI M27-A3 and M38-A2. A total of 67 clinically isolated strains, namely 27 strains of spp., 16 strains of spp., and 24 strains of dematiaceous fungi, were studied. (ATCC 22019) and (ATCC 204304) was included to ensure quality control.
RESULTS
PPIs individually did not exert any significant antifungal activity. The combination of OME with ITC, POS, or VRC showed synergism against 77.6%, 86.6%, and 4% strains of tested pathogenic fungi, respectively, while synergism of OME/FLC was observed in 50% strains of spp. Synergism between PAN and ITC, POS, or VRC was observed against 47.8%, 77.6% and 1.5% strains of tested fungi, respectively, while synergism of PNA/FLC was observed in 50% strains of spp. Synergism of LAN with ITC, POS, or VRC was observed against 86.6%, 86.6%, and 3% of tested strains, respectively, while synergism of LAN/FLC was observed in 31.3% strains of spp. Synergy of the combination of RAB with ITC, POS, or VRC was observed against 25.4%, 64.2%, and 4.5% of tested strains, respectively, while synergism of RAB/FLC was observed in 12.5% of spp.. Among PPIs, synergism was least observed between RAB and triazoles, while among triazoles, synergism was least observed between VRC and PPIs. Among species, synergy was much more frequently observed in spp. and dematiaceous fungi as compared to spp. Antagonism between PPIs with ITC or VRC was occasionally observed in spp. and dematiaceous fungi. It is notable that PPIs combined with azoles showed synergy against azole resistant , and resulted in category change of susceptibility of ITC and POS against spp.
DISCUSSION
The results suggested that PPIs combined with azoles has the potential to enhance the susceptibilities of azoles against multiple pathogenic fungi and could be a promising strategy to overcome azole resistance issues. However, further investigations are warranted to study the combinational efficacy in more isolates and more species, to investigate the underlying mechanism of interaction and to evaluate the potential for concomitant use of these agents in human.
Topics: Humans; Azoles; Proton Pump Inhibitors; Fungi; Antifungal Agents; Triazoles; Voriconazole; Fluconazole; Candida; Aspergillus; Candida parapsilosis; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 38304196
DOI: 10.3389/fcimb.2024.1296151 -
Inflammopharmacology Jun 2024Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the...
Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process.
Topics: Animals; Oxidative Stress; Stomach Ulcer; Rats; Apoptosis; Pantoprazole; Inflammation; Mesenchymal Stem Cells; Male; Mesenchymal Stem Cell Transplantation; Rats, Wistar; Anti-Ulcer Agents; Adipose Tissue; Combined Modality Therapy
PubMed: 38652367
DOI: 10.1007/s10787-024-01469-0