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Spectrochimica Acta. Part A, Molecular... Dec 2023The aim of this study is to develop and validate two simple spectrophotometric methods for simultaneous determination of metoprolol succinate (MET) and olmesartan...
Area under the curve and ratio difference spectrophotometric methods with evaluation of the greenness for simultaneous determination of olmesartan medoxomil and metoprolol succinate.
The aim of this study is to develop and validate two simple spectrophotometric methods for simultaneous determination of metoprolol succinate (MET) and olmesartan medoxomil (OLM) in tablet form. Method (I) was area under the curve (AUC) method. This approach involved the measuring of the area over a variety of wavelengths. Two wavelength ranges; 213-230 nm and 244-266 nm were chosen for determination of MET and OLM, respectively. Method (II) was ratio difference spectrophotometricmethod. For determination of MET, the ratio spectra were generated using 15 μg/mL OLM as a divisor then the peak to trough amplitudes between 221 nm and 245 nm were displayed versus the corresponding concentrations of MET. For determination of OLM, the peak-to-peak amplitudes between 247 and 293 nm were chosen and found to be directly proportional to OLM concentrations using 15 μg/mL MET as a divisor. The linearity ranges were 2-30 μg/mL and 2-25 μg/mL for MET and OLM, respectively. The assay results showed good mean %recovery ± SD as well as good agreement with that of the reported method. The developed methods were validated according to ICH guidelines. The developed methods are accurate, precise, eco-friendly and could be applied successfully to estimate OLM and MET in their combined dosage form.
Topics: Olmesartan Medoxomil; Metoprolol; Spectrophotometry
PubMed: 37499475
DOI: 10.1016/j.saa.2023.123164 -
Annals of Medicine and Surgery (2012) Oct 2023Shensong Yangxin Capsules (SSYX) is a proprietary Chinese medicine commonly, used in the treatment of arrhythmia. In recent years, a flurry of randomized controlled... (Review)
Review
BACKGROUND
Shensong Yangxin Capsules (SSYX) is a proprietary Chinese medicine commonly, used in the treatment of arrhythmia. In recent years, a flurry of randomized controlled trials of SSYX was reported in the treatment of Coronary heart disease arrhythmia in China. However, these experiments have not been systematically evaluated by economics. The purpose of this study was to assess the efficacy, safety, and economy of the SSYX in the treatment of arrhythmia in patients with coronary heart disease.
METHODS
With "Shensong Yangxin Capsules" "Coronary Heart Disease" "Coronary Atherosclerotic Heart Disease"and "Arrhythmia" as the subject words, the relevant journals and conference papers were searched manually in China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP, PubMed, Web Of Science, CBM, Embase and The Cochrane Library. The literature of randomized controlled trials of SSYX in the treatment of coronary heart disease arrhythmia was searched until November 2022. All data were analyzed using RevMan 5.3 Sotware and combined with cost-effectiveness for economic evaluation.
RESULTS
Twenty randomized controlled trials were included in this study, with a total of 2011 cases. The meta-analysis showed that the therapeutic effect of SSYX-metoprolol is superior to that of metoprolol alone. SSYX is superior to amiodarone in improving the total clinical effective rate, reducing the incidence of adverse reactions, and reducing the junction premature beats. There was no significant difference between the SSYX and amiodarone in the curative effect of ECG, ventricular premature complexes, and atrial premature beats. The results of pharmacoeconomics show that SSYX has a cost-effectiveness advantage in treating coronary heart disease arrhythmia. Single-factor sensitivity analysis also confirmed the stability of the results. In summary, SSYX has a curative effect, safety, and economy in treating coronary heart disease arrhythmia.
PubMed: 37811103
DOI: 10.1097/MS9.0000000000001244 -
Pharmaceutics Oct 2023The primary objective of this study was to assess the potential utility of quince seed mucilage as an excipient within a graft copolymer for the development of an...
The primary objective of this study was to assess the potential utility of quince seed mucilage as an excipient within a graft copolymer for the development of an oral-controlled drug delivery system. The -mucilage-based graft copolymer was synthesized via a free radical polymerization method, employing potassium per sulfate (KPS) as the initiator and N, N-methylene bisacrylamide (MBA) as the crosslinker. Various concentrations of monomers, namely acrylic acid (AA) and methacrylic acid (MAA), were used in the graft copolymerization process. Metoprolol tartarate was then incorporated into this graft copolymer matrix, and the resultant drug delivery system was subjected to comprehensive characterization using techniques such as Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The swelling behavior of the drug delivery system was evaluated under different pH conditions, and in vitro drug release studies were conducted. Furthermore, pharmacokinetic parameters including the area under the curve (AUC), maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and half-life (t1/2) were determined for metoprolol-loaded hydrogel formulations in rabbit plasma, and these results were compared with those obtained from a commercially available product. The key findings from the study include observations that higher concentrations of acrylic acid (AA) and mucilage (CM) in the graft copolymer enhanced swelling, while the opposite trend was noted at elevated concentrations of methacrylic acid (MAA) and N, N-methylene bisacrylamide (MBA). FTIR analysis confirmed the formation of the graft copolymer and established the compatibility between the drug and the polymer. SEM imaging revealed a porous structure in the prepared formulations. Additionally, the swelling behavior and drug release profiles indicated a pH-sensitive pattern. The pharmacokinetic assessment revealed sustained release patterns of metoprolol from the hydrogel network system. Notably, the drug-loaded formulation exhibited a higher Cmax (156.48 ng/mL) compared to the marketed metoprolol product (96 ng/mL), and the AUC of the hydrogel-loaded metoprolol was 2.3 times greater than that of the marketed formulation. In conclusion, this study underscores the potential of quince seed mucilage as an intelligent material for graft-copolymer-based oral-controlled release drug delivery systems.
PubMed: 37896205
DOI: 10.3390/pharmaceutics15102445 -
European Journal of Obstetrics,... Aug 2023Is prior beta blocker (BB) use associated with reduced odds of the clinical incidence of leiomyomas?
OBJECTIVE
Is prior beta blocker (BB) use associated with reduced odds of the clinical incidence of leiomyomas?
WHAT IS KNOWN ALREADY
In-vitro and in-vivo evidence has supported the role of beta receptor blockade in reducing leiomyoma cell proliferation and growth. However, no population-based study to date has investigated this potential association.
STUDY DESIGN, SIZE, DURATION
A nested case-control study was conducted in a population of women aged 18-65 with arterial hypertension (n = 699,966). Cases (n = 18,918) with a leiomyoma diagnosis were matched to controls (n = 681,048) with no such diagnosis at a 1:36 ratio by age and region of origin within the United States.
PARTICIPANTS/MATERIALS, SETTING, METHODS
This population was assembled from the Truven Health MarketScan® Research Database, which includes health insurance claims from January 1st, 2012 to December 31st, 2017. Prior use of BB wasdetermined fromoutpatient drug claims and leiomyoma development was indicated by a first-time diagnosis code. We conducted a conditional logistic regression to determine the odds of uterine fibroid development in women with prior use of BB compared to women with no such history. We then conducted subset analyses, stratifying the women by age group and by type of BB.
RESULTS
Women on a BB experienced 15% reduced odds of developing clinically recognized leiomyoma compared to non-users (OR 0.85, 95% CI 0.76-0.94). This association was significant for the 30-39 age group (OR 0.61, 95% CI 0.40-0.93) but no other age group. Of the BBs, propranolol (OR 0.58, 95% CI 0.36-95) demonstrated a significant association with reduced leiomyoma incidence and metoprolol (OR 0.82, 95% CI 0.70-0.97) was associated with lower uterine fibroid incidence after adjustment for comorbidities.
CONCLUSIONS
Hypertensive women with prior BB use experienced reduced odds of developing clinically recognized leiomyoma compared to non-users. A key predisposing risk factor for uterine leiomyoma is elevated blood pressure. Thus, the results of this analysis may have clinical relevance to women with hypertension, as the use of this drug may introduce a dual benefit of managing hypertension as well as curbing an increased risk of leiomyomas.
Topics: Female; Humans; United States; Adult; Infant; Uterine Neoplasms; Case-Control Studies; Incidence; Leiomyoma; Hypertension
PubMed: 37307764
DOI: 10.1016/j.ejogrb.2023.05.028 -
International Journal of Clinical... Feb 2024The aims of this study were to evaluate and compare the pharmacokinetic profiles and establish bioequivalence of test and reference metoprolol succinate extended-release... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
The aims of this study were to evaluate and compare the pharmacokinetic profiles and establish bioequivalence of test and reference metoprolol succinate extended-release (ER) tablets in healthy Chinese subjects under fasting and fed conditions.
MATERIALS AND METHODS
Subjects were randomly assigned to either the fasting or the fed group and also to one of the two treatment sequences (test-reference or reference-test), according to which they received a single 47.5-mg dose of the test or reference metoprolol ER tablet in the study periods. During each period, blood samples were collected at pre-dose and at intervals up to 48 hours after dosing. Plasma concentrations of metoprolol were determined by liquid chromatography. The safety of both ER tablets was monitored throughout the study.
RESULTS
60 subjects were enrolled and all completed the study, with 30 participants each in the fasting and fed groups. In both groups, the 90% confidence intervals for AUC, AUC, and C were within the acceptable bioequivalence range (80 - 125%). There were no significant differences in adverse event (AE) reporting between the subjects receiving test or reference ER tablet. No serious AEs occurred during the study period.
CONCLUSION
The test metoprolol ER tablet was bioequivalent to the reference metoprolol ER tablet (Betaloc ZOK) in healthy Chinese subjects measured under both fasting and fed conditions. Both formulations were well tolerated by all study participants.
Topics: Humans; Therapeutic Equivalency; Metoprolol; Cross-Over Studies; Fasting; Area Under Curve; Healthy Volunteers; Tablets; China
PubMed: 38032146
DOI: 10.5414/CP204474 -
Molecular Pharmaceutics Dec 2023Mucus mechanically protects the intestinal epithelium and impacts the absorption of drugs, with a largely unknown role for bile. We explored the impacts of bile on...
Mucus mechanically protects the intestinal epithelium and impacts the absorption of drugs, with a largely unknown role for bile. We explored the impacts of bile on mucosal biomechanics and drug transport within mucus. Bile diffused with square-root-of-time kinetics and interplayed with mucus, leading to transient stiffening captured in Brillouin images and a concentration-dependent change from subdiffusive to Brownian-like diffusion kinetics within the mucus demonstrated by differential dynamic microscopy. Bile-interacting drugs, Fluphenazine and Perphenazine, diffused faster through mucus in the presence of bile, while Metoprolol, a drug with no bile interaction, displayed consistent diffusion. Our findings were corroborated by rat studies, where co-dosing of a bile acid sequestrant substantially reduced the bioavailability of Perphenazine but not Metoprolol. We clustered over 50 drugs based on their interactions with bile and mucin. Drugs that interacted with bile also interacted with mucin but not vice versa. This study detailed the dynamics of mucus biomechanics under bile exposure and linked the ability of a drug to interact with bile to its abbility to interact with mucus.
Topics: Rats; Animals; Bile; Elevators and Escalators; Perphenazine; Mucus; Mucins
PubMed: 37906224
DOI: 10.1021/acs.molpharmaceut.3c00550 -
Scientific Reports Jul 2023COVID-19 and other acute respiratory viruses can have a long-term impact on health. We aimed to assess the common features and differences in the post-acute phase of...
COVID-19 and other acute respiratory viruses can have a long-term impact on health. We aimed to assess the common features and differences in the post-acute phase of COVID-19 compared with other non-chronic respiratory infections (RESP) using population-based electronic health data. We applied the self-controlled case series method where prescription drugs and health care utilisation were used as indicators of health outcomes during the six-month-long post-acute period. The incidence rate ratios of COVID-19 and RESP groups were compared. The analysis included 146 314 individuals. Out of 5452 drugs analysed, 14 had increased administration after COVID-19 with drugs for cardiovascular diseases (trimetazidine, metoprolol, rosuvastatin) and psychotropic drugs (alprazolam, zolpidem, melatonin) being most prevalent. The health impact of COVID-19 was more apparent among females and individuals with non-severe COVID-19. The increased risk of exacerbating pre-existing conditions was observed for the COVID-19 group. COVID-19 vaccination did not have effect on drug prescriptions but lowered the health care utilisation during post-acute period. Compared with RESP, COVID-19 increased the use of outpatient services during the post-infection period. The long-term negative impact of COVID-19 on life quality must be acknowledged, and supportive health care and public health services provided.
Topics: Female; Humans; COVID-19; Prescription Drugs; COVID-19 Vaccines; Health Services; Delivery of Health Care
PubMed: 37468497
DOI: 10.1038/s41598-023-38691-9 -
Frontiers in Pharmacology 2023Hypertension remains a significant health burden worldwide, re-emphasizing the outstanding need for more effective and safer antihypertensive therapeutic approaches.... (Review)
Review
Hypertension remains a significant health burden worldwide, re-emphasizing the outstanding need for more effective and safer antihypertensive therapeutic approaches. Genetic variation contributes significantly to interindividual variability in treatment response and adverse events, suggesting pharmacogenomics as a major approach to optimize such therapy. This review examines the molecular mechanisms underlying antihypertensives-associated adverse events and surveys existing research on pharmacogenomic biomarkers associated with these events. The current literature revealed limited conclusive evidence supporting the use of genetic variants as reliable indicators of antihypertensive adverse events. However, several noteworthy associations have emerged, such as 1) the role of variants in increasing the risk of multiple adverse events, 2) the bradykinin pathway's involvement in cough induced by ACE inhibitors, and 3) the impact of variants on metoprolol-induced bradycardia. Nonetheless, challenges persist in identifying biomarkers for adverse events across different antihypertensive classes, sometimes due to the rarity of certain events, such as ACE inhibitors-induced angioedema. We also highlight the main limitations of previous studies that warrant attention, including using a targeted gene approach with a limited number of tested variants, small sample sizes, and design issues such as overlooking doses or the time between starting treatment and the onset of adverse events. Addressing these challenges requires collaborative efforts and the integration of technological advancements, such as next-generation sequencing, which can significantly enhance research outcomes and provide the needed evidence. Furthermore, the potential combination of genomic biomarker identification and machine learning is a promising approach for tailoring antihypertensive therapy to individual patients, thereby mitigating the risk of developing adverse events. In conclusion, a deeper understanding of the mechanisms and the pharmacogenomics of adverse events in antihypertensive therapy will likely pave the way for more personalized treatment strategies to improve patient outcomes.
PubMed: 38108069
DOI: 10.3389/fphar.2023.1286494 -
Role of Soil Biofilms in Clogging and Fate of Pharmaceuticals: A Laboratory-Scale Column Experiment.Environmental Science & Technology Aug 2023Contamination of groundwater with pharmaceutical active compounds (PhACs) increased over the last decades. Potential pathways of PhACs to groundwater include techniques...
Contamination of groundwater with pharmaceutical active compounds (PhACs) increased over the last decades. Potential pathways of PhACs to groundwater include techniques such as irrigation, managed aquifer recharge, or bank filtration as well as natural processes such as losing streams of PhACs-loaded source waters. Usually, these systems are characterized by redox-active zones, where microorganisms grow and become immobilized by the formation of biofilms, structures that colonize the pore space and decrease the infiltration capacities, a phenomenon known as bioclogging. The goal of this work is to gain a deeper understanding of the influence of soil biofilms on hydraulic conductivity reduction and the fate of PhACs in the subsurface. For this purpose, we selected three PhACs with different physicochemical properties (carbamazepine, diclofenac, and metoprolol) and performed batch and column experiments using a natural soil, as it is and with the organic matter removed, under different biological conditions. We observed enhanced sorption and biodegradation for all PhACs in the system with higher biological activity. Bioclogging was more prevalent in the absence of organic matter. Our results differ from works using artificial porous media and thus reveal the importance of utilizing natural soils with organic matter in studies designed to assess the role of soil biofilms in bioclogging and the fate of PhACs in soils.
Topics: Soil; Water Pollutants, Chemical; Groundwater; Biodegradation, Environmental; Pharmaceutical Preparations; Biofilms
PubMed: 37558209
DOI: 10.1021/acs.est.3c02034 -
Environmental Pollution (Barking, Essex... Nov 2023Research in the United States evaluating ecotoxic risk to receiving waters posed by contaminants occurring in wastewater discharges typically has focused on measurements...
Research in the United States evaluating ecotoxic risk to receiving waters posed by contaminants occurring in wastewater discharges typically has focused on measurements of pharmaceuticals and personal care products (PPCPs), with limited evaluations of UV filters and phenylpyrazole and neonicotinoid pesticides. In this study, concentrations of 5 representative pharmaceuticals, 11 pesticides or pesticide degradation products, and 5 ultraviolet filters were measured in 24 h composite samples of six wastewater discharges representing ∼70% of the total wastewater discharged to San Francisco Bay during the summer and fall of 2021. No significant difference was observed between concentrations measured on weekdays vs. weekends. A hydrodynamic model of San Francisco Bay was used to estimate annual average dilution factors associated with different subembayments. With and without considering dilution effects, Risk Quotients were calculated using the 90th percentile of measured concentrations in wastewater effluents and threshold concentrations associated with ecotoxicity. Risk Quotients were highest for the neonicotinoid pesticide, imidacloprid, and exceeded ecotoxicity thresholds in the lower South Bay by a factor of 2.4, even when considering dilution. Compared to commonly measured pharmaceuticals, Risk Quotients for imidacloprid were higher than those for carbamazepine, trimethoprim and diclofenac, and comparable to those for propranolol and metoprolol. Risk Quotients for the pesticide, fipronil, and the UV filter, oxybenzone, were higher than for carbamazepine. The results highlight the need to incorporate pesticides and UV filters with high Risk Quotients into studies in the United States evaluating ecotoxic risk associated with contaminants in municipal wastewater discharges.
Topics: Wastewater; Pesticides; San Francisco; Bays; Water Pollutants, Chemical; Environmental Monitoring; Neonicotinoids; Carbamazepine; Pharmaceutical Preparations
PubMed: 37611792
DOI: 10.1016/j.envpol.2023.122432