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Concerns related to environmental risks associated with pharmaceuticals and personal care products (PPCPs) have led researchers to seek methods for assessing and monitoring these contaminants in the aquatic environment. Identifying and validating risk assessment tools that can evaluate ecological concerns and risks associated with PPCPs is critical. Herein, the suitability of a dose-related risk and effect assessment model, which estimates predicted environmental concentrations and allowed comparisons with predicted no effect concentrations determined, in combination with in vitro analyses of the whole effluent toxicity, was verified for the characterization of a PPCP hazard. Concentrations of the most utilized PPCPs in Norway were measured in influent and effluent samples and used to parameterize the fate model. Greater than 90% removal was attained for 12 out of 22 detected PPCPs. Removal was not dependent on the class or the concentration of the specific substance and varied between 12% and 100%. The PPCPs detected in the discharged wastewater were utilized to assess individual contributions to the risk of the effluent, and no risk was identified for the targeted 30 PPCP. The simulations provided valuable information regarding the discharge plume distribution over time, which can aid planning of future environmental monitoring investigations. Bioassays (using fish liver cells, PLHC-1) were used for assessing overall effluent toxicity, through cell viability, production of reactive oxygen species, and ethoxyresorufin-O-deethylase (EROD) activities. The present study may allow regulators to use risk-based strategies over removal criteria for monitoring studies and confirms the importance to take PPCP contamination into consideration when establishing environmental regulations. [ABSTRACT FROM AUTHOR]

Background: Concentrations of metoprolol in exhaled breath condensate (EBC) have not been investigated. Herein, we aim to determine the metoprolol levels in EBC, plasma, and urine samples. Methods: Biological samples were collected from 39 patients receiving metoprolol. Metoprolol was determined using liquid chromatography mass spectrometery. The obtained metoprolol levels in biological fluids were investigated for possible inter-correlations. Results: Acceptable linearity was obtained with coefficient of determinations equal to 0.9998, 0.9941, and 0.9963 for EBC, plasma, and urine samples, respectively. The calibration curves were linear in the ranges of 0.6–500, 0.4–500, and 0.7–10,000 µg·L− 1 regarding EBC, plasma, and urine samples, respectively. The detection and quantification limits were (0.18, 0.12, and 0.21 µg·L− 1) and (0.60, 0.40, and 0.70 µg·L− 1) for EBC, plasma, and urine samples, respectively. The relative standard deviations for the intra- and inter-day replications were obtained between 5.2 and 6.1 and 3.3–4.6%, respectively. The obtained mean metoprolol levels in EBC, plasma, and urine samples of 39 patients were 5.35, 70.76, and 1943.1 µg·L− 1. There were correlations between daily dose and plasma and urinary concentrations of metoprolol in the investigated samples, whereas no significant correlation was observed for daily dose and EBC levels. The correlation among plasma-urine levels was significant, however, the non-significant correlation was obtained between plasma and EBC concentrations. Conclusion: Metoprolol levels varied widely due to the metabolic pattern of the Azeri population, different dosages received by the patients, formulation effects, age, sex, and interactions with the co-administered drugs. A poor correlation of EBC-plasma concentrations and a significant correlation of plasma-urine concentrations were observed. Further investigations are required to provide the updated services to personalized medicine departments. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 35-year-old man who experienced acute myocardial ischemia while using modafinil for depression and Attention-Deficit/Hyperactivity Disorder (ADHD). Topics discussed include the potential cardiovascular risks associated with modafinil, the patient's underlying risk factors such as smoking and alcohol use, and the challenges in determining the exact contribution of modafinil to the ischemic event.

Aim: A validated RP-HPLC method was established for the quantification of Amlodipine and Metoprolol succinate according to ICH guidelines. Materials and Methods: This method utilized a Phenomenex (US) C18 column with dimensions of 250X4.6 mm I.D and a particle size of 5 µm. Employing an isocratic elution technique, the mobile phase comprised pH 3.0 phosphate buffer solution and acetonitrile. Detection occurred at a wavelength of 215 nm and a flow rate of 1 mL/min was chosen to ensure optimal resolution for Amlodipine and Metoprolol succinate. Results and Discussion: Retention times were noted at 3.137 min and 5.672 min for Amlodipine and Metoprolol succinate, respectively. High correlation coefficients were achieved (0.9995 for Amlodipine and 0.9996 for Metoprolol succinate). The method exhibited precision, with low relative standard deviations of 0.357% for Amlodipine and 0.077% for Metoprolol succinate. In summary, the RP-HPLC method developed was specific, linear, precise and robust. Conclusion: The devised method was validated in terms of accuracy, precision, linearity, specificity, robustness and ruggedness. All formulations' sample recoveries were in good accordance with the claims made on their labels. [ABSTRACT FROM AUTHOR]

The aim of the research was to evaluate the influence of antagonists of specific beta-adrenergic receptor subtypes on bowel motility following abdominal surgery in rat model of postoperative ileus. Bowel motility was measured by the intestinal transit of Evans blue introduced via orogastric tube after surgical procedures of skin incision, laparotomy and laparotomy with gut manipulation. Male rats were given individual adrenergic receptor subtypes antagonists intraperitoneally, and the influence of administered agents on intestinal transit of Evans blue was then evaluated. No statistically significant differences in the length of intestine in tested rats were observed. Propranolol administered prior to surgical procedure has shown protective effect on Evans blue migration in rats undergoing laparotomy and gut manipulation. Intestinal dye transit for propranolol doses of 10, 30 and 45 mg/kg was 18.00 ± 1.88c m, 23.75 ± 1.71 cm and 22.5 ± 2.43 cm, respectively, and for last two doses, statistically significant increase of dye passage was noted, compared to Evans blue transit of 11.00 ± 2.43 cm in the control group. No acceleration of dye migration was seen following administration of beta1-, beta2- and beta3-selective adrenergic receptor antagonist metoprolol, ICI 118.551 and SR58894A, respectively. Our research confirmed that propranolol at high doses, as seen by other researchers, improved bowel motility in early phase of postoperative ileus. That slight acceleration of intestinal dye transit after surgery with gut manipulation is rather connected with membrane-stabilizing action, than the receptor blocking effect, as this effect was not observed after the application of selective antagonists of respective subtypes of beta-adrenergic receptor. [ABSTRACT FROM AUTHOR]

Globally, cardio vascular diseases (CVD) remain the primary cause of morbidity and mortality. Pharmacogenomics (PGxs) has profoundly changed how various drug classes are managed in CVDs. For example, genetic polymorphisms in genes such as SLCO1B1 impact how a person responds to statins such as rosuvastatin and atorvastatin, where as the interindividual variability in the reaction to statins (Fluvastatin)used in lipid-lowering therapy can be partly explained by genetic variations in genes encoding drug-metabolizing enzymes such cytochrome P450 and transporters like OATP1B1. Similarly, in antiplatelet therapy, polymorphisms in CYP2C19 affect clopidogrel metabolism, influencing its efficacy in preventing thrombotic events. Genes such as CYP2C9 and VKORC1 are crucial for the metabolism and response to acenocoumarol and warfarin during anticoagulant therapy and monitoring bleeding risk. Genetic variations in CYP2D6 affect the metabolism and effectiveness of propafenone and metoprolol. Understanding the PGx presumptions of these cardiovascular drugs may help develop personalized treatment strategies that lower the possibility of adverse drug reactions, obtain desired therapeutic outcomes, and improve patient compliance and safety with respect to each patient’s unique genetic makeup.

Aim: The present study compared the safety, efficacy, and tolerability of the new fixed-dose combination (FDC) of telmisartan 40 mg + bisoprolol 5 mg (TBP) tablets with the existing comparator FDC telmisartan 40 mg + metoprolol succinate ER 50 mg (TMS) tablets in patients with stage 1 and stage 2 hypertension. Methodology: The multicentric, double-blind, parallel-group, comparative, prospective, phase-III clinical study involved 264 subjects with stage 1 and stage 2 hypertension from 10 centres across India. The selected subjects were randomized into two groups: group A received the TMS and group B received the new FDC TBP. The primary endpoint was the mean change in seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) from baseline to week 12 in both the control and study arms. The secondary endpoint was achieving the target of SeSBP

Drug release plays a crucial role in drug delivery. While current formulation approaches are capable of coarse-tuning the release profile, their precision and reproducibility are limited by the physicochemical properties of the excipients and active pharmaceutical ingredient (API). Innovative and advanced approaches are urgently needed, especially for site-specific targeting of drugs and to address their pharmacological requirements for optimal therapy. The 5 × 5 × 0.6 mm3 piezoelectric micropump developed by Fraunhofer EMFT was designed to enable precise drug delivery in a low volume format. In this study, we investigated the ability of the micropump to deliver solutions of highly soluble APIs using a wide range of customized pump profiles. Additionally, we examined the ability of the micropump to deliver suspensions containing various defined particle sizes. While results for suspensions indicate that pumping performance is highly dependent on the size and concentration of the suspended particles, results with API solutions demonstrate high precision and reproducibility of release, coupled with maximum flexibility in the release profile of the API. The piezoelectric micropump thus lays the cornerstone in the development of a wide range of innovative drug delivery profiles, enabling customized release profiles to be programmed and thus paving the way to fully personalized medicine. [Display omitted] [ABSTRACT FROM AUTHOR]

A method for quantification of antihypertensive drugs (lisinopril, indapamide, metoprolol, valsartan, and amlodipine) in human blood serum was developed using high-performance liquid chromatography with tandem mass spectrometric detection (HPLC-MS/MS). MeOH with added fexofenadine hydrochloride as an internal standard was used for sample preparation. The developed method was validated for the following parameters: selectivity, limit of quantitation, linearity, intra- and inter-run accuracy and precision, sample transfer, matrix effect, extraction effect, and sample stability. The analytical range of the method for all analytes was 1 – 1000 ng/mL, which made it possible to assess the patient adherence to treatment and conduct therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

The article discusses the results of the REDUCE-AMI trial, which compared the efficacy of long-term beta-blocker therapy versus no therapy in patients with acute myocardial infarction and preserved ejection fraction. It is reported that the study found no significant differences in the primary endpoint of all-cause mortality and recurrent myocardial infarction between the two groups.

In this work, a new electrochemical sensor for the detection of the doping agent metoprolol (MTP) in food samples and bodily fluids is presented. The sensor's foundation is a nanocomposite made of polypyrrole (PPy) and nickel oxide nanoparticles (NiO NPs) on a glassy carbon electrode (GCE). Pyrole was electropolymerized to create the nanocomposite, and then NiO NPs were electrodedeposited on the GCE surface (NiO NPs/PPy/GCE). By combining the benefits of PPy with NiO NPs, this technique offers good electrocatalytic activity and a large surface area for analyte interaction. The nanocomposite was characterized using structural analyses such as scanning electron microscopy (SEM), X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS). These analyses revealed a network-like structure that improved the accessibility of the electrolyte ions and showed that the nanocomposite had been successfully deposited on the GCE surface. The electrochemical MTP sensor was examined using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) tests. The sensor's sensitivity was 0.03074 μA/μM, and it demonstrated a linear connection between the peak currents and the MTP concentrations (5–1600μM). The suggested sensor's limit of quantification (LOQ) and limit of detection (LOD) were determined to be 0.581 μM and 0.018 μM, respectively. The prepared urine sample produced acceptable recovery rates in the range of 98.40–99.86% in the real sample analyses, together with low relative standard deviation values (below 4.16%). In a similar vein, the prepared apple juice sample analysis revealed low relative standard deviation values (less than 4.28%) and respectable recovery rates ranging from 97.20 to 99.66%. The results showed low relative standard deviation values and good recovery rates, demonstrating the high precision and dependability of the suggested approach. [ABSTRACT FROM AUTHOR]

The analytical community prioritizes adopting green techniques due to concerns over the environmental impact of chemical research. This study employs an integrated experimental strategy, combining the concept of design of experiment (DOE) and green analytical chemistry (GAC), to establish a robust, green RP-HPLC approach for the simultaneous estimation Cilnidipine (CIL) and Metoprolol succinate (MET). For method optimization, a central composite design (CCD) was implemented. Separation utilized Inertsil ODS 3 column (250 mm x 4.6 mm, 5 μm), with gradient mobile phase (ethanol: 17.65% at 0 min, 75.5% at 3 min) and phosphate buffer, flowing at 1 ml/ min. Detection wavelength at 230 nm. Column temperature (35±1°C), and injection volume 5 μL. Retention times: MET (4.672 min), CIL (7.457 min). The linearity was established over the range of 7-13 μg/ml for CIL and 35-65 μg/ml for MET. The values obtained for LOD and LOQ are 0.819 and 2.482 μg/ml (CIL) respectively, 3.875 and 11.743 μg/ml (MET). As per ICH Q14, the technique has been validated. Finally the green nature was examined by GAPI, AES and AGREE. Method found to be ecofriendly, simple and robust for simultaneous CIL and MET estimation in pharmaceutical formulations, easily adaptable for routine analysis. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (MI) is a common and severe cardiovascular emergency that requires immediate treatment. Angina pectoris, which typically signals myocardial ischaemia, can appear in MI cases with myriad causes aside from coronary artery disease. However, not all MI patients benefit from invasive revascularisation therapy. We herein report a case involving a 78-year-old female patient with a complex medical history, including non-ST-segment elevation MI and coronary artery bypass grafting, who experienced recurrent chest pain. Instead of a direct result of coronary artery disease, her chest pain was later found to be primarily induced by atrial fibrillation (AF). Consequently, we shifted the focus of management to effective rate control for the AF after careful evaluation and achieved a satisfactory result. This case highlights the successful identification and timely application of intensive heart rate control management in an MI case induced by AF. [ABSTRACT FROM AUTHOR]

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Carvedilol can inhibit inflammation, vasoconstriction, and oxidative stress, which play important roles in the development and progression of contrast-induced nephropathy (CIN). To the best of our knowledge, no studies have investigated the potential effect of carvedilol on the prevalence of CIN after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). The present study aimed to determine whether carvedilol use is associated with the development of CIN. A total of 319 patients (mean age, 59.2 ± 12.4 years; 77.7% male) with ACS who underwent urgent PCI at our institution between May 2019 and May 2022 were included prospectively. Overall, 100 and 219 patients were assigned to the carvedilol and metoprolol groups, respectively. The prevalence of CIN was significantly lower in the carvedilol group (6.0%) than in the metoprolol group (18.3%; P =.003). Multivariate analysis revealed that carvedilol use (odds ratio [OR].250, 95% confidence interval [CI].092-.677, P =.006), amount of contrast agent (OR 1.004, 95% CI 1.000-1.008, P =.031), and admission estimated glomerular filtration rate (OR.978, 95% CI 0.960-.995, P =.014) were independently associated with the development of CIN. The use of carvedilol may be a promising option for the prevention of CIN in patients with ACS undergoing urgent PCI. [ABSTRACT FROM AUTHOR]

Owing to the complex lifestyle of the current generation and the nature of disease burden, the extensive use of selective β–blockers have increased. Although many β–blockers are considered safe for ingestion via different routes, in some cases, ingestion can lead to fatal doses. However, postmortem analysis of these materials is limited to body fluid, and the use of visceral samples has not yet been explored. In this paper, we successfully extracted metoprolol from visceral samples. The quantification of extracted metoprolol from Viscera-I and Viscera-II was carried out using the GC‒MS-SIM method. The quantity of metoprolol used in the Viscera-I and Viscera-II groups was 10.58 mg and 1.14 mg per 100 g of visceral sample, respectively. The quantity obtained correlated with the constituents of the body organs in Viscera-I and Viscera-II. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) is a serious heart ailment that requires cutting-edge remedies for effective treatment. This study examines the possible cardioprotective effects of a hydroalcoholic extract from Satureja hortensis L. (HASH) in rats with isoproterenol (ISO) induced myocardial infarction. Methods: The rats were pretreated orally with hydroalcoholic extract of Satureja hortensis low (200 mg/kg), high dose (400 mg/kg), and metoprolol (10 mg/kg), in their respective groups for 30 days, followed by two subcutaneous doses of isoproterenol (ISO). Blood was obtained to measure biochemicals such as creatine kinase-MB (CK-MB), Troponin I, Alanine transaminase (ALT), Aspartate transaminase (AST), and lactate dehydrogenase (LDH), and an electrocardiogram (ECG) of a rat was recorded after the experiment. Myocardial integrity was examined histopathologically, and malondialdehyde (MDA) levels and antioxidant enzyme concentrations were assessed using heart tissue homogenate. Results: Rats with myocardial infarction caused by ISO displayed significantly (P