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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 -
Frontiers in Pharmacology 2023The aim was to systematically compare the drug compatibility with various closed intravenous (i.v.) infusion containers, to provide a reference for selecting a...
The aim was to systematically compare the drug compatibility with various closed intravenous (i.v.) infusion containers, to provide a reference for selecting a relatively superior infusion container and improve the medication safety for patients in clinical practice. The compatibility of four commonly used clinical injections (ceftazidime, pantoprazole sodium, ambroxol hydrochloride, edaravone) with three representative closed i. v. infusion containers (non-PVC infusion bags, upright polypropylene infusion bags, inner sealed polypropylene infusion bags) prefilled with infusion fluids (0.9% sodium chloride or 5% dextrose) in the Chinese market were investigated in this study. The particle counts of both infusion fluids and diluted chemical injections by infusion fluids in various infusion containers were determined by the light obscuration method. At 0, 2 and 6 h after four injections following dilution with infusion fluids in each container, the pH of the solutions was detected, and the physical properties were examined by visual inspection. Meanwhile, the drug concentrations were assessed by high performance liquid chromatography (HPLC). As for either infusion fluids or diluted injections by infusion fluids, the particle counts in non-PVC infusion bags were significantly greater than those in the other two bags under some circumstances. The particle counts in diluted injections by infusion fluids increased dramatically compared with those in infusion fluids in all infusion containers, especially for the small-size particles. But pH, physical properties and drug concentrations of diluted infusion solutions in all infusion containers remained nearly unchanged over the test period. Closed i. v. infusion containers included in this study are all well-compatible with four injections. Moreover, the closed infusion containers produced by Chinese manufacturers have met the international quality standard. Particularly, the intravenous admixture preparation process needs to be optimized to reduce the overall particulate contaminants.
PubMed: 38259265
DOI: 10.3389/fphar.2023.1265945 -
Molecular Biology Reports Mar 2024Gastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore...
BACKGROUND
Gastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved.
METHODS
An ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done.
RESULTS
The ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group.
CONCLUSIONS
Aloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.
Topics: Rats; Male; Animals; Stomach Ulcer; Antioxidants; NLR Family, Pyrin Domain-Containing 3 Protein; Ethanol; Ulcer; Gastrins; Pyroptosis; Rats, Wistar; Plant Extracts; Signal Transduction; Plant Preparations
PubMed: 38457071
DOI: 10.1007/s11033-024-09329-4 -
Cancer Investigation Sep 2023This study aimed to reveal the drug-repurposing candidates for colorectal cancer (CRC) drug-repurposing methods and network biology approaches. A novel, differentially...
This study aimed to reveal the drug-repurposing candidates for colorectal cancer (CRC) drug-repurposing methods and network biology approaches. A novel, differentially co-expressed, highly interconnected, and co-regulated prognostic gene module was identified for CRC. Based on the gene module, polyethylene glycol (PEG), gallic acid, pyrazole, cordycepin, phenothiazine, pantoprazole, cysteamine, indisulam, valinomycin, trametinib, BRD-K81473043, AZD8055, dovitinib, BRD-A17065207, and tyrphostin AG1478 presented as drugs and small molecule candidates previously studied in the CRC. Lornoxicam, suxamethonium, oprelvekin, sirukumab, levetiracetam, sulpiride, NVP-TAE684, AS605240, 480743.cdx, HDAC6 inhibitor ISOX, BRD-K03829970, and L-6307 are proposed as novel drugs and small molecule candidates for CRC.
Topics: Humans; Drug Repositioning; Colorectal Neoplasms; Gene Regulatory Networks; Prognosis; Computational Biology
PubMed: 37682113
DOI: 10.1080/07357907.2023.2255672 -
Igiene E Sanita Pubblica 2024BACKGROUND This study aimed to investigate, among elderly patients in long-term care (LTC) facilities, potentially inappropriate drug prescriptions, potentially...
BACKGROUND This study aimed to investigate, among elderly patients in long-term care (LTC) facilities, potentially inappropriate drug prescriptions, potentially interactions and verify whether they can be traced back to hospitalisations or accesses to the Emergency Department (ED). The study data were acquired by means of a case report form investigating the medication management process in LTCs. MATERIAL AND METHODS Analysis of pharmacutilisation in LTCFs patients aged ≥65 years on polypharmacy or excessive polypharmacy, January-July 2023. Data was extracted from a database (DB) containing the monthly prescriptions of medicines supplied by direct distribution (DD) to LTCs. The prevalence of PIMs was evaluated by applying the Beers and STOPP criteria to the medication profile of each patient. RESULTS The overall prevalence of polypharmacy and hyperpolypharmacy was 83% and 17%, respectively. PIMs were defined using Beers and STOPP criteria. The most frequent PIMs were proton pump inhibitors (19% e 15%), antiplatelets agent (17% e 13%) and non-associated sulfonamides (14% e 12%). Of the 1,921 PIMs, 121 were contraindicated or very serious (6%) and 1,800 were major (94%).The most common medicaments involved in drug-drug interaction are furosemide (21%), sertraline (19%), pantoprazole (16%) e trazodone (15%). LTCs participating in the study (56%) excluded polypharmacy as a cause of access to the ED and ADRs. Therefore no case was ever reported (100%). CONCLUSIONS Polypharmacy or excessive polypharmacy among elderly patients may increase PIMs and ADRs. A constant review of the therapeutic regimens and deprescribing decrease inappropriate use of medications and interactions, ADRs, and accesses to the ED with consequent reduction of pharmaceutical spending.
Topics: Humans; Aged; Retrospective Studies; Inappropriate Prescribing; Long-Term Care; Polypharmacy; Female; Male; Aged, 80 and over; Italy; Potentially Inappropriate Medication List; Drug Interactions; Hospitalization
PubMed: 38708444
DOI: No ID Found -
Journal of Clinical Medicine May 2024: To define if the use of proton pump inhibitors (PPI) is associated with PDF prevalence and characteristics and with time of recovery after dialysis in patients on...
: To define if the use of proton pump inhibitors (PPI) is associated with PDF prevalence and characteristics and with time of recovery after dialysis in patients on maintenance hemodialysis. : Patients were defined as experiencing PDF if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Time of recovery after dialysis (TIRD) was also assessed for each patient. Each patient was invited to rate the intensity, duration and frequency of PDF from 1 to 5. We defined if patients used PPI (no PPI use or PPI use), the type of used PPI, the dose of used PPI, and the duration of the use of PPI (<1 year or ≥1 year). : A total of 346 patients were studied: 259 used PPI (55 used omeprazole, 63 esomeprazole, 54 pantoprazole, 87 lansoprazole, and 7 rabeprazole) and 87 did not. Two hundred and thirty-two patients declared PDF and 114 did not. The median [min-max] TIRD was 210 min [0-1440]. The prevalence of PDF in PPI users and PPI non-users was 67% and 68%, respectively ( = 0.878). The median [min-max] TIRD did not differ significantly between PPI users and PPI non-users (180 [0-1440] and 240 [0-1440], respectively; = 0.871). Median PDF intensity, duration, frequency, and severity did not differ significantly between PPI use and no use. The prevalence of PDF was similar among the different types of PPI use and did not differ with respect to PPI non-users. Duration of PPI exposure was <1 year in 40 patients and ≥1 year in 219 patients. The prevalence of PDF did not differ between the two exposures. The correlation matrix between PPI equivalent dose, PPI treatment duration and PDF frequency, PDF characteristics, and TIRD showed whether there was statistical significance. : The use of PPI is not associated with PDF and time of recovery after dialysis in patients on maintenance hemodialysis.
PubMed: 38892950
DOI: 10.3390/jcm13113241 -
Acta Medica Portuguesa Apr 2024
Topics: Humans; Pantoprazole; Diabetic Ketoacidosis; Chemical and Drug Induced Liver Injury, Chronic; Proton Pump Inhibitors; Diabetes Mellitus
PubMed: 38631049
DOI: 10.20344/amp.20928 -
Hospital Pharmacy Apr 2024Accuracy of medication charts on admission to hospital has previously shown that inadvertent omission of therapy was the most common discrepancy, accounting for 40% to...
Accuracy of medication charts on admission to hospital has previously shown that inadvertent omission of therapy was the most common discrepancy, accounting for 40% to 60% of errors. Partnered Pharmacist Medication Charting (PPMC) has shown to reduce medicationrelated problems. The aim of this study was to evaluate the implementation of Pharmacist Medication Charting (PMC), a derivative of PPMC, in a maternity and gynecological hospital. The occurrence of medication omission identified by the pharmacists was assessed and the pharmacist interventions involving PMC analyzed. The pharmacist interventions documented from 1st July 2022 to 30th June, 2023 were evaluated using PowerBI for data and trends on the Medication-Related Problems (MRPs) identified, occurrence of PMC, common medications charted by the pharmacists and the pharmacist recommendation and action following the identification of MRPs. A total of 4898 pharmacy interventions was documented in the 12-month period. Of the total interventions documented, 1321 (26.97%) were related to pharmacist medication charting. Of all the interventions related to PMC, 53.29% involved pharmacists charting medications for the continuation or initiation of over-the-counter medications, 13.32% involved pharmacist partnered charting of Prescription Only Medications and Controlled Medications with medical staff, and 33.3% were referred to a credentialled pharmacist for PMC service. With regards to action taken following interventions involving PMC, 1065 (80.62%) were resolved following PMC. Common medications charted by the pharmacists include: macrogol and docusate laxatives (288), pregnancy multivitamin containing iron, iodine and folate (169), colecalciferol (133), iron (127), asthma inhaler (99), paracetamol and ibuprofen (88), nicotine (38), calcium (29), folic acid (26), and pantoprazole (15). Our study demonstrated that hospital pharmacists contribute to the reduction of MRPs, and PMC enables pharmacist to address prescribing omission and conditions untreated in the hospital. This study also reflects skills enhancement in practice for clinical pharmacists and resulted in successful implementation of PMC.
PubMed: 38450359
DOI: 10.1177/00185787231207752 -
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 -
F1000Research 2023Enteric coating films in acidic labile tablets protect the drug molecule from the acidic environment of the stomach. However, variations in the excipients used in the...
Enteric coating films in acidic labile tablets protect the drug molecule from the acidic environment of the stomach. However, variations in the excipients used in the coating formulation may affect their ability to provide adequate protection. This study is the first to investigate the potential effects of coating materials on the protective functionality of enteric coating films for pantoprazole (PNZ) generic tablets after their recall from the market. A comparative analysis was conducted between generic and branded PNZ products, using pure drug powder for identification. The release of the drug was evaluated in different pH media. The study also utilized various analytical and thermal techniques, including differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and confocal Raman microscopy. The assessment results revealed significant variations in the release profile for the generic product in acidic media at 120 min. DSC and TGA thermal profile analyses showed slight variation between the two products. XRD analysis exhibited a noticeable difference in peak intensity for the generic sample, while SEM revealed smaller particle sizes in the generic product. The obtained spectra profile for the generic product displayed significant variation in peaks and band intensity, possibly due to impurities. These findings suggest that the excipients used in the enteric coating film of the generic product may have affected its protective functionality, leading to premature drug release in acidic media. Additionally, the presence of polysorbate 80 (P-80) in the brand product might improve the properties of the enteric coating film due to its multi-functionality. : In conclusion, the excipients used in the brand product demonstrated superior functionality in effectively protecting the drug molecule from acidic media through the enteric coating film, as compared to the generic version.
Topics: Pantoprazole; Drug Liberation; Excipients; Solubility; Tablets; Stomach
PubMed: 38596002
DOI: 10.12688/f1000research.140607.1