Search

Background and Purpose: This study analyses whether first‐line antihypertensive drugs ameliorate the dysbiosis state in hypertension, and to test if this modification contributes to their blood pressure (BP) lowering properties in a genetic model of neurogenic hypertension. Experimental Approach: Twenty‐week‐old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were untreated or treated with captopril, amlodipine or hydrochlorothiazide. A faecal microbiota transplantation (FMT) experiment was also performed by gavage of faecal content from donor SHR‐treated groups to SHR recipients for 3 weeks. Key results: Faeces from SHR showed gut dysbiosis, characterized by lower acetate‐ and higher lactate‐producing bacteria and lower strict anaerobic bacteria. All three drugs increased the anaerobic bacteria proportion, captopril and amlodipine restored the proportion of acetate‐producing bacterial populations to WKY levels, whereas hydrochlorothiazide decreased butyrate‐producing bacteria. Captopril and amlodipine decreased gut pathology and permeability and attenuated sympathetic drive in the gut. Both drugs decreased neuroinflammation and oxidative stress in the hypothalamic paraventricular nuclei. Hydrochlorothiazide was unable to reduce neuroinflammation, gut sympathetic tone and gut integrity. FMT from SHR‐amlodipine to SHR decreased BP, ameliorated aortic endothelium‐dependent relaxation to acetylcholine, lowered NADPH oxidase activity, aortic Th17 infiltration and reduced neuroinflammation, whereas FMT from SHR‐hydrochlorothiazide did not have these effects. Conclusions and Implications: First‐line antihypertensive drugs induced different modifications of gut integrity and gut dysbiosis in SHR, which result in no contribution of microbiota in the BP lowering effects of hydrochlorothiazide, whereas the vasculo‐protective effect induced by amlodipine involves gut microbiota reshaping and gut‐immune system communication. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases, especially hypertension, stand as prominent contributors to global mortality. Hypertension, often referred to as a silent killer syndrome, necessitates the use of multiple medications for effective control and management. A new environmentally friendly HPLC–DAD method is introduced in this study for the concurrent analysis of telmisartan (TEL), chlorthalidone (CHT) and amlodipine besylate (AML), in both pure forms and combined pharmaceutical dosage form. An isocratic elution mode was employed to achieve chromatographic separation, utilizing an Inertsil C18 column (250 × 4.6 mm, 5.0 µm) and a mobile phase mixture of acetonitrile and phosphate buffer (pH 3.0 ± 0.1) with ratio of 35:65, v/v. The separation was achieved within 10 min at a flow rate of 1.0 mL/min. The proposed method's validation was carried out following the guidelines outlined by the International Council for Harmonisation (ICH). The achieved linearity range was 1.0–140.0 μg/mL for TEL and 1.0–100.0 μg/mL for CHT and AML with quantification limits of 0.061, 0.177, and 0.313 μg/mL for TEL, CHT, and AML, respectively. The fixed combination tablet dosage form demonstrated acceptable release profile, as indicated by the in-vitro dissolution studies. The studied dissolution media were phosphate buffer pH 7.5, 0.01 N HCl, and water, utilizing a USP type II apparatus at 37 ± 0.5 °C with a stirring rate of 75 rpm. The proposed method was applied successfully for the quality assessment of Telma-ACT® Tablets with good precision and accuracy. Various tools were used for evaluating the level of greenness, including Green Analytical Procedure Index (GAPI), Analytical Greenness Metric for Sample Preparation (AGREEprep), Analytical Eco-Scale (AES), and Analytical Method Greenness Score (AMGS). These tools had confirmed the eco-friendliness of the proposed method. Additionally, the newly introduced White Analytical Chemistry (WAC), and the Blue Applicability Grade Index (BAGI) have been specifically developed to evaluate the sustainability and the applicability of the method. [ABSTRACT FROM AUTHOR]

Firstly, the SiO2 microspheres were prepared by Stӧber method, and then modified by 3-Aminopropyltrimethoxysilane (KH-540) to introduce –NH2 onto the microspheres. Then, SiO2-NH2 microspheres were mixed into polysulfone casting solution, and SiO2-NH2/PSF composite membrane was prepared by the phase conversion method. On this basis, the functional adsorbent SiO2-NH2/PSF-g-PMAA was prepared by grafting polymerization of methacrylic acid (MAA) as a functional monomer using –NH2/S2O82− surface initiation system. The samples were characterized by Fourier infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), the Brunauer–Emmett–Teller (BET) and weighing method. The adsorption properties of amlodipine (ADP) by functional adsorbents were investigated, and the adsorption mechanism was further studied. The results show that the adsorption reaches equilibrium at 180 min, and the adsorption kinetics can be well fitted by the pseudo-second-order model. The adsorption capacity of SiO2-NH2/PSF-g-PMAA for amlodipine in methanol with 1.4 mg/mL at 15 °C is 137 mg/g. The adsorption ability increases with the decrease of ionic strength and temperature via the hydrogen bond and ionic interactions, and the adsorption of ADP by SiO2-NH2/PSF-g-PMAA is consistent with the D-R adsorption isotherm model. Thermodynamic parameters imply that adsorption is a spontaneous and exothermic process. [ABSTRACT FROM AUTHOR]

Objectives: Hypertension is one of the major modifiable risk factors for cardiovascular mortality and morbidity throughout the world. Increased life expectancy leads to increase prevalence of non‐communicable diseases among the elderly people including Bangladesh. However, different studies reported high prevalence of uncontrolled hypertension ranging from 52.6% to 67.9% among the elderly people in different countries. With this view, we aimed to assess the frequency of uncontrolled blood pressure (BP) among the elderly hypertensive people and its associated risk factors and treatment pattern in Bangladesh. Methodology: This cross‐sectional type of observational study recruited 246 eligible hypertensive elderly patients attending in 250 Bedded General Hospital, Jashore, Bangladesh dated from 1st July to 31st December 2022. A structured questionnaire was developed and data on associated risk factors, treatment pattern and current blood pressure (BP) measurement were collected by face‐to‐face interview for the purposive sampling technique. Results: The mean age of our study patients was 72 ± 7 years with a male and female ratio nearly 1:1. Of the total hypertensive patients aged over 65 years or more, 56.5% remained with uncontrolled hypertension even on their prescribed antihypertensive medications. The mean systolic (SBP) and diastolic (DBP) blood pressure were significantly high (P < 0.001) as 167 ± 22 mm Hg and 95 ± 11 mm Hg, respectively, among the uncontrolled hypertensive patients. However, we noticed the mean SBP and DBP among the total hypertensive patients were also significantly high (P < 0.001) as 148 ± 27 mm Hg and 87 ± 13 mm Hg, respectively. In this study, we reported that the mean number of last prescribed antihypertensive medications used by the total patients was 2 ± 1 (P =0.224) which was similar among the controlled and uncontrolled hypertensive patient groups. Among the elderly hypertensive patients, the most commonly prescribed antihypertensive medications were Amlodipine 39.8% (P =0.006), Olmesartan 29.3% (P = 0.186), Losartan 24.4% (P = 0.127), Bisoprolol 15.0% (P = 0.266) and Atenolol 14.6% (P = 0.224). Conclusion: We noticed high frequency of uncontrolled blood pressure among the elderly hypertensive patients, despite of using multiple antihypertensive medications in Jashore, Bangladesh. [ABSTRACT FROM AUTHOR]

This study aimed to identify risk factors for amlodipine-induced gingival enlargement, assess quality of life, and analyze gingival tissue. This cross-sectional study involved hypertensive patients on amlodipine, divided into groups with and without gingival enlargement. Assessments included sociodemographic data, clinical evaluations, and clinical parameters. Quality of life was assessed using OHIP-14 and WB-HRQoL scales. Gingival tissue samples were analyzed for oxidative status and key molecules using RT-PCR and colorimetric assays. The study included 32 patients with no significant sociodemographic differences between groups (p > 0.05). Patients with gingival enlargement had higher systolic blood pressure (139.63 ± 10.743 vs. 128.38 ± 7.249, p = 0.028) and higher OHIP-14 scores. The RT-PCR analysis showed significant differences in IL-6, TNF-α, IL-33, ST2, TGF-β1, FGF-2, CTGF, VEGF-D, and KGF expression. IL-6, TNF-α, ST2, and FGF-2 expression levels were lower in patients taking amlodipine, with and without gingival enlargement. TGF-β1 and CTGF expression levels were highest in patients with amlodipine-induced gingival enlargement. SOD activity was also highest in these patients, whereas MDA levels were higher in patients with gingival enlargement without amlodipine. Our study highlights the impact of amlodipine-induced gingival enlargement on oral health and quality of life, emphasizing fibrosis and oxidative stress, and suggests the need for integrated healthcare approaches and further research. [ABSTRACT FROM AUTHOR]

Objective: Dihydropyridine calcium channel blocker (DHP-CCBs) is an appropriate add-on antihypertensive option for uncontrolled blood pressure diabetic hypertensive patients with albuminuria who are already taking renin-angiotensin system blockers (RASBs). Among DHP-CCBs, amlodipine is the first-line medication in combination with RASBs. However, new-generation DHP-CCBs like lercanidipine has demonstrated superior effectiveness and fewer side effects, although at a higher cost than amlodipine. This study aims to assess the cost-effectiveness of lercanidipine versus amlodipine when added to RASBs in diabetic hypertensive patients with albuminuria. The objective is to provide robust evidence guiding the selection of the most suitable and worthwhile treatment option in Thailand. Materials and Methods: This study analyses the cost-effectiveness of lercanidipine versus amlodipine as an addition to RASBs in diabetic hypertensive patients with albuminuria. The analysis was conducted from a societal perspective using a Markov model. Results: The total costs of lercanidipine and amlodipine treatments were 370,392.83 baht and 384,221.85 baht, respectively. The life years gained for lercanidipine and amlodipine treatments were 11.33 years and 10.96 years respectively. Additionally, the quality-adjusted life years (QALYs) of lercanidipine and amlodipine treatments were 8.06 years and 7.51 years respectively. The calculated ICER was negative, indicating treatment with lercanidipine as a dominant strategy. Conclusion: Due to lercanidipine’s noticeable cost-effectiveness, lower costs, and longer QALYs. Adding lercanidipine has proven to be more cost-effective than amlodipine for diabetic hypertensive patients with albuminuria who have been unable to achieve their blood pressure goals with RASBs alone. Therefore, lercanidipine should be the preferred choice as an add-on to RASBs in Thailand. These results could significantly aid policymakers in making informed decisions. [ABSTRACT FROM AUTHOR]

Background: Dispensed drugs stored by patients are often in single-dose packages (SDPs) or are crushed and mixed after being removed from a press-through package (PTP) sheet. Information on their stability is extremely limited. To address this, we explored using chemiluminescence (CL) measurements to detect oxidative degradation. Methods: Eight amlodipine, 14 telmisartan, and two warfarin preparations were used as specimens. These preparations were stored at room temperature under various conditions, after which CL was measured. Cellopoly packaging paper was used for SDP. Three light conditions were used (Condition A: darkness, Condition B: indoor diffused light (approximately 400 lx), and Condition C: exposure to 4,000 lx). CL cumulative light output was measured every minute under nitrogen gas conduction and with a sample chamber temperature of 150 °C, for a maximum of 10 min. Luminescence images were obtained simultaneously with the CL measurements. Results: CL was observed on light-exposed tablet surfaces. For each preparation, an increase in the CL value was observed with the duration of light exposure. In the same preparation with the same exposure time, CL tended to be higher in the order of Condition A < B < C. Moreover, CL increased even when no changes in color were observed by the naked eye. A comparison between preparations with the same main ingredients showed differences in the rate of increase in CL with exposure, and each was found to show a different reactivity to light. Conclusions: To the best of our knowledge, this is the first study to visually capture the surface oxidation of tablets exposed to light using the CL method. The CL values, thought to be derived from photooxidation, increased with exposure of tablets and powders to light after SDP. This method can sensitively assess drug degradation due to photooxidation. Further research is needed to establish a CL method for assessing the stability of preparations in clinical settings. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course. Background: Amlodipine, a calcium channel blocker, and atenolol, a beta blocker, are commonly used as a fixed drug combination (FDC) to treat hypertension. Intentional or non-intentional overdose of amlodipine-atenolol results in hypotension and myocardial depression with a high risk of mortality. This report describes a 64-year-old man with an overdose of amlodipine-atenolol, presenting as an emergency with hypotension, bradycardia, and severe metabolic acidosis. He was successfully treated with intravenous calcium chloride infusion, hyperinsulinemia euglycemia therapy (HIE), and continuous veno-venous hemodialysis (CVVHD). Case Report: A 64-year-old man was diagnosed with essential hypertension 1 week prior to the admission. He had been prescribed 1 FDC tablet of amlodipine and atenolol (5+50 mg) per day; however, he took 1 table of the FDC per day for 3 days and then took 3-4 tablets each day during the next 4 days. He was brought to the hospital with hypotension, bradycardia, and severe metabolic acidosis and was diagnosed with amlodipine-atenolol overdose. He was treated with intravenous calcium chloride infusion, HIE, and CVVHD. His hemodynamics started to improve after administering these therapies for 6 h. Inotropes were gradually tapered off and stopped. He was extubated on day 5 and recovered completely. Conclusions: This report shows the serious effects amlodipine-atenolol overdose and the challenges of emergency patient management. An overdose of FDC of amlodipine and atenolol can cause cardiovascular collapse and severe metabolic acidosis. Timely and aggressive management with intravenous calcium infusion, HIE, and CVVHD is essential. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a condition when blood pressure increases or is often referred to as a “silent killer” because signs and sympotoms occur, usually causing headaches, nosebleeds, irreguler heartbead, fan buzzing in the ears, hypertension is a disease that is often found among elderly. Research Purposes: To determine the effect of patients taking amlodipine on urea levels. Research Methodos: Analytic observational research with cross sectional research design. Used 24 sampels of hypertension who consumend the drug amlodipine and analyzed the data using a non parametric test. Result: The mean results of examining urea levels in patients taking amlodipine were 31,61. Conclusion: There was a significant effect of patients taking the drug amlodipine on urea levels according to adherence in taking the a p value of 0,003 (p<0,05). The results of blood pressure meansurements of patients taking the drug averaged 145 mg/dl. [ABSTRACT FROM AUTHOR]

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]

Introduction: Fixed-dose combinations (FDCs) of angiotensin II receptor blockers, calcium channel blockers, and statins are conventional therapeutic interventions prescribed for cardiovascular diseases. This study aimed at drawing a comparison between the pharmacokinetics and safety of an FDC and the corresponding individual formulations in healthy subjects. Methods: A randomized, open-label, single-dose, three-sequence, three-period, partially repeated crossover study was conducted with a cohort of healthy volunteers. A 14-day washout period was maintained between each of the three periods. In this study, candesartan cilexetil, amlodipine, and atorvastatin was administered orally as FDCs of 16/10/40 mg in study 1 and 16/5/20 mg in study 2. The maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from time zero to the time of the last quantifiable concentration (AUClast) of candesartan, amlodipine, and atorvastatin were estimated as the geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the FDC to individual formulations. If the within-subject coefficient of variation (CVwr) of Cmax was greater than 0.3, the bioequivalence (BE) range calculated using the reference-scaled average bioequivalence was used to assess whether the 90% CI was within the BE range. Results: The GMRs (90% CIs) for the AUClast for candesartan and amlodipine were 0.9612 (0.9158–1.0089)/0.9965 (0.9550–1.0397) and 1.0033 (0.9800–1.0271)/1.0067 (0.9798–1.0344), and the GMRs (90% CIs) for Cmax were 0.9600 (0.8953–1.0294)/0.9851 (0.9368–1.0359) and 1.0198 (0.9950–1.0453)/1.0003 (0.9694–1.0321) in studies 1 and 2, respectively. The extended BE ranges calculated from the CVwr of the Cmax of atorvastatin were 0.7814–1.2797 and 0.7415–1.3485, respectively. The GMRs (90% CIs) for the AUClast of atorvastatin were 1.0532 (1.0082–1.1003)/1.0252 (0.9841–1.0680), and the GMRs (90% CIs) for Cmax were 1.0630 (0.9418–1.1997)/0.9888 (0.8792–1.1120) in studies 1 and 2, respectively. Conclusion: The Cmax and AUClast values of candesartan cilexetil/amlodipine/atorvastatin 16/10/40 mg and 16/5/20 mg, respectively, were within the BE ranges. There were no clinically significant differences in safety between the two formulations. Trial Registration: ClinicalTrials.gov identifier, study 1: NCT04478097; study 2: NCT04627207. [ABSTRACT FROM AUTHOR]

Amlodipine (AM) is a long active calcium channel blocker used to relax blood vessels by preventing calcium ion transport into the vascular walls and its supporting molecules acetaminophen (AP) and ascorbic acid (AA) are recommended for hypertension control and prevention. Considering their therapeutic importance and potential side effects due to over dosage, we have fabricated a sensor for individual and simultaneous determination of AA, AP, and AM in pharmaceuticals and human urine using novel Zn-doped Ca2CuO3 nanoparticles modified glassy carbon electrode (GCE). Optimally doped Ca2CuO3 (2.5 wt% Zn at Cu site) enhanced the detection of target molecules over much wider concentration ranges of 50 to 3130 µM for AA, 0.25 to 417 µM for AP, and 0.8 to 354 µM for AM with the corresponding lowest detection limits of 14 µM, 0.05 µM, and 0.07 µM, respectively. Furthermore, the Zn-Ca2CuO3/GCE exhibited excellent selectivity and high sensitivity even in the presence of several potential interfering agents. The usefulness of the developed electrode was tested using an amlodipine besylate tablet and urine samples of seven hypertension patients under medication. The results confirmed the presence of a significant amount of AP and AM in six patients' urine samples indicating that the personalized medication is essential and the quantum of medication need to be fixed by knowing the excess medicines excreted through urine. Thus, the Zn-Ca2CuO3/GCE with a high recovery percentage and good sensitivity shall be useful in the pharmaceutical and biomedical sectors. [ABSTRACT FROM AUTHOR]

Background: Uncontrolled blood pressure is a major risk factor for cardiovascular diseases. Fixed-dose combination (FDC) therapy offers a promising approach to addressing this challenge by providing a convenient single-tablet solution that enhances the effectiveness of blood pressure control. In our systematic review, we assess the effectiveness of perindopril/amlodipine FDC in managing blood pressure. Methods: We conducted a comprehensive search across four primary electronic databases, namely, PubMed, Virtual Health Library (VHL), Global Health Library (GHL), and Google Scholar, as of 8 February 2022. Additionally, we performed a manual search to find relevant articles. The quality of the selected articles was evaluated using the Study Quality Assessment Tools (SQAT) checklist from the National Institute of Health and the ROB2 tool from Cochrane. Results: Our systematic review included 17 eligible articles. The findings show that the use of perindopril/amlodipine FDC significantly lowers blood pressure and enhances the quality of blood pressure control. Compared to the comparison group, the perindopril/amlodipine combination tablet resulted in a higher rate of blood pressure response and normalization. Importantly, perindopril/amlodipine FDC contributes to improved patient adherence with minimal side effects. However, studies conducted to date have not provided assessments of the cost-effectiveness of perindopril/amlodipine FDC. Conclusion: In summary, our analysis confirms the effectiveness of perindopril/amlodipine FDC in lowering blood pressure, with combination therapy outperforming monotherapy and placebo. Although mild adverse reactions were observed in a small subset of participants, cost-effectiveness assessments for this treatment remain lacking in the literature. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) remains a leading cause of cancer mortality globally. Synaptotagmin-4 (SYT4), a calcium-sensing synaptic vesicle protein, has been implicated in the oncogenesis of diverse malignancies. Purpose: This study delineates the role of SYT4 in modulating clinical outcomes and biological behaviors in GC. Methods: We evaluated SYT4 expression in GC specimens using bioinformatics analyses and immunohistochemistry. Functional assays included CCK8 proliferation tests, apoptosis assays via flow cytometry, confocal calcium imaging, and xenograft models. Western blotting elucidated MAPK pathway involvement. Additionally, we investigated the impact of the calcium channel blocker amlodipine on cellular dynamics and MAPK pathway activity. Results: SYT4 was higher in GC tissues, and the elevated SYT4 was significantly correlated with adverse prognosis. Both univariate and multivariate analyses confirmed SYT4 as an independent prognostic indicator for GC. Functionally, SYT4 promoted tumorigenesis by fostering cellular proliferation, inhibiting apoptosis, and enhancing intracellular Ca2+ influx, predominantly via MAPK pathway activation. Amlodipine pre-treatment attenuated SYT4-driven cell growth and potentiated apoptosis, corroborated by in vivo xenograft assessments. These effects were attributed to MAPK pathway suppression by amlodipine. Conclusion: SYT4 emerges as a potential prognostic biomarker and a pro-oncogenic mediator in GC through a Ca2+-dependent MAPK mechanism. Amlodipine demonstrates significant antitumor effects against SYT4-driven GC, positing its therapeutic promise. This study underscores the imperative of targeting calcium signaling in GC treatment strategies. [ABSTRACT FROM AUTHOR]

Background and Objective: This study aimed to assess and compare the pharmacokinetics, safety, and tolerability of a fixed-dose combination product (FDCP) comprising four different drugs (two antihypertensive drugs, amlodipine and losartan, and two lipid-lowering agents, ezetimibe and rosuvastatin) with their separate tablets. Methods: A total of 60 participants were enrolled in this open-label, randomized, single-dose crossover study. Each participant received a single dose of FDCP and individual tablets during each period, with a 14-day washout period between the periods. The pharmacokinetic parameters of amlodipine, losartan, EXP3174 (an active metabolite of losartan), rosuvastatin, free ezetimibe, and total ezetimibe were evaluated and compared. Results: The pharmacokinetic profiles of amlodipine, losartan, rosuvastatin, and ezetimibe after administration of the individual products were similar to those of FDCP. The geometric mean ratios and 90% confidence intervals for maximum concentration (Cmax) and area under the curve (AUC) of FDCP to individual tablets were within 0.8–1.25 for all six analytes. No clinically relevant changes were observed in the vital signs or physical, biochemical, hematological, electrocardiographic, or urinalysis findings during the study, and no serious adverse events were reported. Conclusion: This study demonstrated that a newly developed FDCP containing amlodipine, losartan, ezetimibe, and rosuvastatin exhibited pharmacokinetic equivalence with the individual products and met the regulatory criteria. Both formulations were well tolerated. Clinical Trial Registration: This trial (NCT04322266) was retrospectively registered on 9 September 2019. [ABSTRACT FROM AUTHOR]

Introduction: Worldwide, arterial hypertension is the foremost preventable and modifiable cardiovascular risk factor. In addition to lifestyle changes, recent international guidelines recommend single-pill, low-dose combinations as initial treatment strategy. We investigated whether this approach is feasible in a rural sub-Saharan Africa setting. Methods: Diagnosis of hypertension was established over three sets of blood pressure measurements, performed according to the European Society of Hypertension recommendations by trained personnel, using a validated, automated, oscillometric device OMRON M7 IT-HEM-7322-E. In 98 individuals with arterial hypertension, a once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide was prescribed at an appropriate dose. Patients were instructed on its administration and potential side effects and encouraged towards lifestyle modifications. The treatment regimen was adjusted, if needed, at each outpatient clinic scheduled after 4, 8, 12, and 16 weeks. Results: Seventy-nine patients (aged 61 [53–70] years; median and interquartile range) strictly adhered to the treatment schedule, while 19 individuals (70 [65–80] years) dropped out. Blood pressure was < 140/90 mmHg after 4 weeks in 44 (56%), after 8 weeks in 62 (78%), after 12 weeks in 69 (87%), and after 16 weeks in 74 (94%) participants. Excellent tolerance was reported. Conclusions: These results provide real-life evidence that hypertension management with a once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide as initial treatment is feasible and effective also in a rural sub-Saharan setting. Single-pill combinations should be made available also in rural and remote areas in low- and middle-income countries as a reliable first-line treatment strategy. [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]

Fixed-dose combination therapy is considered a practical approach in the treatment of various diseases, as it can simultaneously target different mechanisms of action that achieve the required therapeutic efficacy through a synergistic effect. A combination of hydrochlorothiazide (HTZ), amlodipine (AMD), and valsartan (VLS) has been created for the treatment of hypertension. Therefore, the aim of this study was to develop an optimized UPLC method for the simultaneous quantification of this combination. A DoE at a level of 32 was used to investigate the effects of column temperature (20, 30, and 40 °C) and formic acid concentration (0.05, 0.15, and 0.25%) on the retention time of each active pharmaceutical ingredient (API), the peak area, and the peak symmetry, as well as the resolution between HTZ-AMD and AMD-VLS peaks. The optimized analytical method was validated and used to extract the three APIs from the marketed product. The optimized analytical condition with a column temperature of 27.86 °C and a formic acid concentration of 0.172% showed good separation of the three APIs in 1.62 ± 0.006, 3.59 ± 0.002, and 3.94 ± 0.002 min for HTZ, AMD, and VST, respectively. The developed method was linear with the LOQ for a HTC, AMD, and VST of 0.028, 0.038, and 0.101 ppm, respectively. Moreover, the developed assay was sustainable and robust, with an RSD % of less than 2%. The application of this method in the extraction of HTZ, AMD, and VST from the Exforge® marketed product showed good separation with a measurable drug content of 23.5 ± 0.7, 9.68 ± 0.1, and 165.2 ± 5.2 mg compared to the label claims of 25/10/160 for HTZ, AMD, and VST, respectively. [ABSTRACT FROM AUTHOR]

Acute high-output heart failure (HOHF) with pulmonary hypertension and liver injury caused by amlodipine poisoning is very rare. We report a 52-year-old woman who suffered from severe shock after an overdose of amlodipine. Hemodynamic monitoring showed that while her left ventricular systolic function and cardiac output were elevated, her systemic vascular resistance decreased significantly. At the same time, the size of her right heart, her central venous pressure, and the oxygen saturation of her central venous circulation all increased abnormally. The patient's circulatory function and right ventricular dysfunction gradually improved after large doses of vasopressors and detoxification measures. However, her bilirubin and transaminase levels increased significantly on hospital day 6, with a CT scan showing patchy, low-density areas in her liver along with ascites. After liver protective treatment and plasma exchange, the patient's liver function gradually recovered. A CT scan 4 months later showed all her liver abnormalities, including ascites, had resolved. The common etiologies of HOHF were excluded in this case, and significantly reduced systemic vascular resistance caused by amlodipine overdose was thought to be the primary pathophysiological basis of HOHF. The significant increase in venous return and pulmonary blood flow is considered to be the main mechanism of right ventricular dysfunction and pulmonary hypertension. Hypoxic hepatitis caused by a combination of hepatic congestion and distributive shock may be the most important factors causing liver injury in this patient. Whether amlodipine has other mechanisms leading to HOHF and pulmonary hypertension needs to be further studied. Considering the significant increase of right heart preload, aggressive fluid resuscitation should be done very cautiously in patients with HOHF and shock secondary to amlodipine overdose. [ABSTRACT FROM AUTHOR]

The investigation of the real-world use of the extemporaneous combination of nebivolol and amlodipine (NA-EXC) in adult patients diagnosed with hypertension in Europe. Retrospective analysis of data extracted from seven databases of patient medical records and prescriptions from Italy, Germany, France, Hungary, and Poland, to determine the prevalence and incidence of NA-EXC use and to estimate the number of patients potentially eligible for a single-pill combination of the two antihypertensives. Secondary objectives included: the description of the population of NA-EXC users and the assessment of their adherence to treatment based on the proportion of days covered. The use of NA-EXC was found to be common in Europe and ranged between 2.9% to 9.9% of all patients identified in the databases with a prescription of nebivolol and/or amlodipine. The estimated numbers of patients potentially eligible in 2019 for a single-pill combination of nebivolol and amlodipine in Italy and Germany were, respectively, 178,133 and 113,240. Users of NA-EXC were mostly aged 70–79 years, had metabolic disorders and other comorbidities; >70% of them had received ≥2 concomitant medications before starting NA-EXC. Adherence to NA-EXC was defined as high only in 15.6% to 35% of patients. The extemporaneous combination of nebivolol and amlodipine is commonly prescribed in Europe, however adherence to the therapy is poor. The development of a single-pill combination of nebivolol and amlodipine may improve adherence by reducing the number of pills administered to patients and thus simplifying treatment regimens. [ABSTRACT FROM AUTHOR]

Tyrosinase (TYR) inhibitors are very significant as they inhibit enzyme tyrosinase activity, and its inhibition is vital for skin care, anticancer medication, and antibrowning of fruits and vegetables. This work presents a novel and economical route for the preparation of new synthetic tyrosinase inhibitors using amlodipine (4). The novel conjugates 6 (a–o) were designed, synthesized, and characterized by spectroscopic analyses, including Fourier transform infrared and low- and high-resolution mass spectroscopy. The purified compound 4 was refluxed with various aldehydes and ketones 5 (a–o) for 5–8 h in methanol at 60°C–90°C. This research modified the drug in a step-by-step manner to develop therapeutic properties as a tyrosinase inhibitor. The structures of synthesized ligands 6 (a–o) were established based on spectral and analytical data. The synthesized compounds 6 (a–o) were screened against tyrosinase enzyme. Kojic acid was taken as standard. All the prepared compounds 6 (a–o) have good inhibition potential against the enzyme tyrosinase. Compounds 6o, 6b, 6f, and 6k depicted excellent antityrosinase activity. Compound 6k, with an IC50 value of 5.34 ± 0.58 µM, is as potent as the standard kojic acid (IC50 6.04 ± 0.11 µM), standing out among all synthesized compounds 6 (a–o). The in silico studies of the conjugates 6 (a–o) were evaluated via PatchDock. Compound 6k showed a binding affinity score of 8,999 and an atomic contact energy (ACE) value of −219.66 kcal/mol. The structure–activity relationship illustrated that the presence of dihydropyridine nuclei and some activating groups at the ortho and para positions of the benzylideneimine moiety is the main factor for good tyrosinase activity. The compound 6k could be used as a lead compound for drug modification as a tyrosinase inhibitor for skin care, anticancer medication, and antibrowning for fruits and vegetables. [ABSTRACT FROM AUTHOR]

Background: Oral Thin Film (OTF) is an emerging approach for oral drug delivery but still there exists a scarcity of evidence for formulation optimization techniques. Herein, we aim to develop OTFs optimized by the QbD approach. Materials and Methods: OTFs were prepared by solvent casting method using Amlodipine as an active ingredient and excipients such as Pectin, Aspartame, Tween 80, and Glycerine. The developed formulation was optimized using QbD software Design Expert version 8.0.4, USA. The independent variables of the experiment were selected as A-pectin, B-Tween-80, and C-glycerine, and the dependent variables were R1-tensile strength (kg/cm2), R2-permeation rate (µg/cm2/hr), R3-disintegration time (in a sec). Finally, the software suggested optimized formulation based on a desirability value closer to 1. Results: The optimized oral films were comparatively evaluated and characterized by various techniques. The drug release was found to be ~96% at 10 min for OTFs and ~94% at 20 min for oral fast-dissolving tablets. The amlodipine was scanned in the UV range of 200 to 400 nm and the λmax was observed to be at 240±2 in a Phosphate of pH 6.8. Conclusion: All results are found satisfactory and well within the acceptance range. This ensures that similar formulations can be optimized by using this technique in the future. [ABSTRACT FROM AUTHOR]

In the current work, the solubility of amlodipine besylate (ADB) was studied in the ethylene glycol + ethanol at different temperatures (293.2-313.2 K). The experimental solubility data obtained herein were correlated with some well-known cosolvency models and the accuracy of these models was investigated with the mean relative deviations of the back calculated data. The apparent thermodynamic parameters (Gibbs energy, enthalpy and entropy) of ADB in the non-aqueous saturated mixtures were also calculated with the van't Hoff and Gibbs equations at Thm. [ABSTRACT FROM AUTHOR]

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca2+) and other metal ions, such as zinc (Zn2+) and magnesium (Mg2+), into the cytosol. This Ca2+ influx at the presynaptic terminal triggers the release of Zn2+ and glutamate to the postsynaptic terminal. Zn2+ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn2+ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn2+ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn2+ accumulation, oxidative stress, and neuronal death. Our findings show that AML's LTCC inhibition decreased excessive Zn2+ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine's potential as a therapeutic agent in seizure management and mitigating seizures' detrimental effects. [ABSTRACT FROM AUTHOR]

Introduction: Calcium channel blockers (CCB) are a leading cause of ingestion-associated fatality. Angiotensin-converting enzyme inhibitor (ACEi) overdose as part of co-ingestion is common and associated with refractory shock. Treatment options to manage this profound vasoplegia are limited. We describe the first case of use of newly formulated Angiotensin II for treatment of severe ACEi and CCB poisoning. Case Report: A 57-year-old man presented after suicide attempt by ingesting 20 tablets each of amlodipine 10 mg and benazepril 20 mg. His hypotension was initially managed with 35 mL/kg of crystalloid, norepinephrine, and hyperinsulinemic euglycemic therapy (HIET). His hemodynamics further deteriorated, and he developed lactic acidosis, electrolyte derangements, and renal dysfunction. Further complications of his ingestion included cardiac arrest, subsequent requirement for emergency cricothyrotomy, and renal replacement therapy. Maximal hemodynamic support with HIET therapy insulin drip 4.4 units/kg/hour, norepinephrine 2 mcg/kg/min, epinephrine 1 mcg/kg/min, vasopressin.06 units/hour, and intravenous lipid emulsion was unsuccessful. Ang II was started and titrated to maximal doses with dramatic improvement in hemodynamics. Within hours of starting Ang II, epinephrine was stopped and norepinephrine decreased by 50%. He was downgraded from the intensive care unit without any ongoing end-organ dysfunction. Discussion: Isolated CCB overdoses have high complication rates and well-established treatments. Therefore, management of CCB and ACEi co-ingestion is typically driven by CCB poisoning algorithm. There are multiple reports of CCB and ACEi co-ingestions causing treatment-refractory shock. Therapeutic options are limited by toxicities and availability of salvage therapies. Ang II is a safe and highly effective option to manage these patients. [ABSTRACT FROM AUTHOR]

Introduction: Acute coronary syndrome, chronic forms of ischemic heart disease (IHD) and postinfarction cardiosclerosis are the main causes of morbidity and mortality in the world, including Russia. In the XXI century, there is an increase in comorbid pathology, especially in the combination of IHD with arterial hypertension, diabetes, chronic obstructive pulmonary disease and chronic kidney disease. Patients with IHD and chronic kidney disease have a higher incidence of coronary events and complications. The frequency of coronary events and complications indicates the need to improve the diagnosis and treatment of this group of patients. diagnosis and treatment of this group of patients. The aim of the study was to analyze the dynamics of vascular stiffness, pulmonary hypertension (PH), diastolic heart dysfunction and endothelial dysfunction indices in patients with different variants of ischemic heart disease combined with chronic kidney disease (CKD) stage 1-3 using complex therapy of combined hypotensive drug Amlodipine/ Indapamide/Perindopril three months after coronary stenting and to compare them with the group of patients on conservative therapy only. Material and Methods: 85 patients with different forms of IHD, arterial hypertension (AH) on the background of CKD 1-3 stages, as well as data of 42 patients with IHD, AH without renal pathology were analyzed. The first group -- IHD, postinfarction cardiosclerosis, CKD stage 1-3 (33 patients); the second group -- acute coronary syndrome with ST-segment elevation, Myocardial infarction (MI) (30 patients); the third group -- ACS without ST-segment elevation, Unstable angina (UA) (22 patients). Results: The highest indices of vascular stiffness (Pulse wave velocity (PWV), Augmentation index (AI), CAVI, Central Systolic Blood Pressure (SBPao), central arterial pulse pressure (PP)) were registered in combination of ACS with ST-segment elevation and CKD 1-3 stages. These indices are markers of IHD progression in these patients; they also have increased pulmonary hypertension and diastolic dysfunction of the heart, endothelial dysfunction with vasodilation insufficiency in 88% of cases, which even without hemodynamically significant coronary artery stenoses according to coronary CT angiography data leads to the development of ACS with ST-segment elevation and ACS without ST-segment elevation with MI. Copyright: © Sergey A. Pribylov et al. Amlodipine/Indapamide/Perindopril was prescribed to all patients due to high arterial hypertension on admission against the background of basic therapy of IHD and coronary stenting. Coronary CT angiography in patients with comorbid renal pathology does not lead to aggravation of chronic kidney disease after 3 months, on the contrary; in this group of patients the most pronounced decrease of arterial stiffness (AS), AI, SBPao, PP with elevation of glomerular filtration rate (GFR) and decrease of creatinine in blood occurs in comparison with the group of patients who did not undergo coronary stenting, they were only on conservative therapy. Conclusion: Prescription of three component drug Amlodipine/Indapamide/Perindopril on the background of baseline therapy especially in combination with surgical vascularization of the heart is justified. [ABSTRACT FROM AUTHOR]

The incidence of paediatric obesity continues to rise worldwide and contributes to a range of diseases including cardiovascular disease. Obesity in children has been shown to impact upon the plasma concentrations of various compounds, including amlodipine. Nonetheless, information on the influence of obesity on amlodipine pharmacokinetics and the need for dose adjustment has not been studied previously. This study applied the physiologically based pharmacokinetic modelling and established a paediatric obesity population to assess the impact of obesity on amlodipine pharmacokinetics in children and explore the possible dose adjustments required to reach the same plasma concentration as non-obese paediatrics. The difference in predicted maximum concentration (Cmax) and area under the curve (AUC) were significant between children with and without obesity across the age group 2 to 18 years old when a fixed-dose regimen was used. On the contrary, a weight-based dose regimen showed no difference in Cmax between obese and non-obese from 2 to 9 years old. Thus, when a fixed-dose regimen is to be administered, a 1.25- to 1.5-fold increase in dose is required in obese children to achieve the same Cmax concentration as non-obese children, specifically for children aged 5 years and above. [ABSTRACT FROM AUTHOR]

Background Amlodipine is the most commonly prescribed calcium channel blocker (CCB), used in the treatment of a variety of cardiovascular conditions. Calcium channel blockers remain a well-established cause of cardiovascular drug overdose. We present the case of an intentional overdose with 250 mg of amlodipine resulting in acute left ventricular dysfunction and myocarditis. Case summary A 46-year-old man with no significant past medical history presented to the emergency department 8 h after intentionally ingesting 250 mg of amlodipine. Although initially asymptomatic with unremarkable physical examination, the patient developed progressively worsening dyspnoea over the next 2 days. Subsequent findings from chest X-ray, electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging (MRI) were consistent with a diffuse myocarditis process with severe left ventricular systolic dysfunction. The patient was managed with diuretics and discharged once stable. Discussion Our case highlights myocarditis as a potential complication of CCB overdose. Amlodipine is the most commonly prescribed CCB and is associated with cardiac toxicity at high doses. The long duration of action and high volume of distribution of amlodipine further increase the risk of morbidity and mortality from overdose. Known cardiac complications of amlodipine overdose include bradycardia, myocardial depression, and pulmonary oedema secondary to heart failure; however, diffuse myocarditis is a complication that has not previously been described in the literature. The mechanism of development of this complication remains unclear. [ABSTRACT FROM AUTHOR]

This study aims to assess clinical outcomes following switching from originator to generic amlodipine. This population‐based, matched, cohort study included users of originator amlodipine using claims data during 2018–2020 from a health system in Tianjin, China, in which usage of generic amlodipine was promoted by a drug procurement policy, the national volume‐based procurement. Non‐switchers refer to those remained on originator after the policy, while pure‐switchers were those who switched to and continued using generic amlodipine, and back‐switchers were those switched to generic amlodipine but then back to the originator. Propensity score matching generates comparable non‐switchers and pure‐switchers pairs, and non‐switchers and back‐switchers pairs. The primary outcome was major adverse cardiovascular events (MACEs), defined as all‐cause mortality, stroke, and myocardial infarction during follow‐up (April 1, 2019 to December 30, 2020). Secondary outcomes included heart failure, atrial fibrillation, and adherence to amlodipine. The hazard ratio (HR) for each clinical outcome was assessed through Cox proportional hazard regression. In total, 5943 non‐switchers, 2949 pure‐switchers, and 3061 back‐switchers were included (mean age: 62.9 years; 55.5% men). For the matched pairs, pure‐switchers (N = 2180) presented no additional risks of clinical outcomes compared to non‐switchers (N = 4360) (e.g., MACEs: 2.86 vs. 2.95 events per 100 person‐years; HR = 0.97 [95%CI: 0.70–1.33]). Back‐switchers (N = 1998) also presented no additional risk compared to non‐switchers (N = 3996) for most outcomes except for stroke (HR = 1.55 [95%CI: 1.03–2.34]). Pure‐switchers and back‐switchers all had better amlodipine adherence than non‐switchers. Generic substitution of amlodipine is not associated with increased risk of cardiovascular events or all‐cause mortality, but improves medicine adherence. [ABSTRACT FROM AUTHOR]

In this study, two polyelectrolytes, chitosan and propyl methyl cellulose carbonate, were associated by crosslinking with tripolyphosphate (TPP), to prepare microspheres loaded with amlodipine besylate (Aml). The formulations were optimized by Box–Behnken experimental design, in which three factors, four responses were studied to check the effect of independent variables (concentration of TPP, pH of TPP solution, and pH of a polymer mixture) on responses: zeta potential, particle size, polydispersity index and entrapment efficiency. The optimal encapsulation efficiency was around 92.43%, the zeta potential on average 41.75 mV, and the minimum mean particle size was 310 nm. The effects of the parameters on changes in structure, crystallinity, and surface charges of polymers, by crosslinking in microparticles, were identified by FT-IR, XRD, and dynamic light scattering analyses. The encapsulation parameters and the environment media influenced the mechanism of release and the kinetics model, which was greater in the duodenal medium at pH 5.5 (Q = 100%). The microencapsulation by nontoxic polymers in water is a good method of preparing amlodipine-loaded microspheres, which are intended for the oral route, with optimal dose release in the duodenal medium. This represents the target site for absorption of the drug, in the pulmonary sphere. [ABSTRACT FROM AUTHOR]

Hypertension is defined as a systolic blood pressure (SBP) of 140 mm Hg or more, or a diastolic blood pressure (DBP) of 90 mm Hg or more. Globally, an estimated 26% of the world's population (972 million people) has hypertension, and the prevalence is expected to increase to 29% by 2025, driven largely by increase in economically developing nations. Hypertension affects one in four individuals worldwide. ARBs, CCBs are first line of therapy of hypertension and has out shifted the use of ACEIs. Telmisartan is the preferable ARB, Amlodipine a third generation CCB are commonly prescribed for hypertension in INDIA. Telmisartan has a very high lipophilicity and high volume of distribution which offers advantage of good tissue penetration over other sartans. Amlodipine a DHPs of CCBs is prescribed because of less negative inotropic and high vascular selectivity. The present study comprises of 60 patients (both men and women) of 18 and above age, who are suffering from idiopathic hypertension to know the efficacy of low dose combination therapy of Telmisartan(40mg) with Amlodipine (5mg) against high dose monotherapy of Telmisartan(80mg). In present study, a low dose combination therapy of Telmisartan 40mg + Amlodipine 5mg has demonstrated significantly greater BP reduction in both SBP and DBP compared to high dose monotherapy with Telmisartan 80mg. The combination therapy with Telmisartan 40mg + Amlodipine 5mg is well tolerated with a safety profile similar to the monotherapy with Telmisartan 80mg. [ABSTRACT FROM AUTHOR]

Buccal lichenoid lesions (BLLs) are characterised by a unique, linear whitish striation in the buccal region and can be accompanied by ulcers, plaques, erythemas, atrophies and blisters. They are distinguished from oral lichen planus (OLP) by the association of the administration of a drug or contact with a metal. Herein, we present the case of a 42-year-old woman with underlying hypertension with amlodipine-induced BLLs. She complained of a 1-month history of right buccal whitish streaks and oral ulcers 2 months after taking amlodipine. She visited a private otorhinolaryngology clinic, and a biopsy for the right buccal ulcer was conducted. The biopsy result showed features suggestive of OLP. The patient was then diagnosed with OLP. Her symptoms were persistent despite treatment, so a dental referral was made. Amlodipine was suspected as the cause of her condition and was therefore stopped. Her condition gradually resolved after amlodipine withdrawal. Hence, primary care physicians should be aware of BLLs as one of the adverse drug reactions of amlodipine so that prompt management can be taken to avoid further debilitating impacts on patients. [ABSTRACT FROM AUTHOR]

Arteriovenous malformations (AVMs) are a tangle of blood vessels that connects arteries and veins in which the feeding arteries are directly connected to the venous channels. Cerebral AVM needs special consideration due to high risk of bleeding and neurological deficit associated with morbidity and mortality. In pediatric population, prevalence rate of cerebral AVM is 0.02%. The systemic hemodynamic changes are seen more frequently with peripheral AVM, whereas its association with cerebral AVM is rare. We report a rare case of cerebral AVM in a 12-year-old child with severe systemic hypertension and electrocardiogram changes of biventricular hypertrophy planned for surgical resection of AVM in view of intracerebral bleed. This case illustrates the importance of detailed cardiac, renal, and endocrine evaluation in children with cerebral AVM with systemic hypertension and left ventricular hypertrophy to rule out other causes of systemic hypertension prior to surgery. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the blood concentration and pharmacokinetic (PK) parameters of 2 formulations under fasting and ed conditions in healthy Chinese volunteers and to evaluate whether the 2 preparations were bioequivalent. This trial screened 170 subjects. Thirteen subjects were assigned to the fasting trial and 18 subjects to the fed trial; 1 subject in the fed trial group was automatically withdrawn for personal reasons. Two cycles had a 14‐day washout period. This clinical study was a bioequivalence study, with PK parameters as end point indicators. The bioequivalence PK parameters were the maximal concentration (Cmax), area under the blood drug concentration‐time curve from 0 to 72 hours (AUC0‐72 h), and the time to peak plasma concentration (tmax) which were determined in human plasma by the liquid chromatography‐tandem mass spectrometry method, and nonatrioventricular model analysis was used to determine Cmax, AUC0‐72 h, tmax, and other PK parameters. The incidence of adverse events was calculated on the basis of System Organ Classification and Preferred Terms. The results showed that the amlodipine besylate tablets met the equivalence range requirements of bioequivalence in the guidelines for human bioavailability and bioequivalence testing under fasting and fed conditions, compared to the fasting test; the tmax of the fed test was almost unchanged; and the Cmax and AUC0‐72 h showed no difference between fasting and fed conditions. It was confirmed that both formulations were well tolerated, and no new safety signals were observed. [ABSTRACT FROM AUTHOR]

Background: Systemic hypertension (SH) is a common cardiovascular disease in older cats that is treated primarily with the calcium channel blocker amlodipine besylate (AML). The systemic effect of AML on the classical and alterative arms of the renin‐angiotensin‐aldosterone system (RAAS) in cats is incompletely characterized. Hypothesis/Objectives: To determine the effect of AML compared to placebo on circulating RAAS biomarkers in healthy cats using RAAS fingerprinting. Animals: Twenty healthy client‐owned cats. Methods: Cats were administered amlodipine besylate (0.625 mg in toto) or placebo by mouth once daily for 14 days in a crossover design with a 4‐week washout period. Plasma AML concentrations and RAAS biomarker concentrations were measured at multiple timepoints after the final dose in each treatment period. Time‐weighted averages for RAAS biomarkers over 24 hours after dosing were compared between treatment groups using Wilcoxon rank‐sum testing. Results: Compared to placebo, AML treatment was associated with increases in markers of plasma renin concentration (median 44% increase; interquartile range [IQR] 19%‐86%; P =.009), angiotensin I (59% increase; IQR 27‐101%; P =.006), angiotensin II (56% increase; IQR 5‐70%; P =.023), angiotensin IV (42% increase; −19% to 89%; P =.013); and angiotensin 1‐7 (38% increase; IQR 9‐118%; P =.015). Conclusions and Clinical Importance: In healthy cats, administration of AML resulted in nonspecific activation of both classical and alternative RAAS pathways. [ABSTRACT FROM AUTHOR]

Background: Little evidence exists about the comparative effects of first‐line antihypertensive medications (i.e., renin‐angiotensin‐aldosterone converting enzyme inhibitors (RAASi), amlodipine, or thiazide diuretics) in older adults with limited life expectancy. We compared the rates of injurious falls and short‐term cardiovascular events between different first‐line antihypertensive medication classes in adults receiving care in nursing homes (NH). Methods: This was a retrospective cohort of Medicare fee‐for‐service beneficiaries receiving care in NHs. Patients newly dispensed first‐line antihypertensive medications were identified using Part D claims (2015–2018) and linked with clinical assessments (i.e., Minimum Data Set). Fall‐related injuries (FRI), hip fractures, and major adverse cardiac events (MACE) outcomes were identified using hospitalization claims. Patients were followed from the date of antihypertensive dispensing until the occurrence of outcomes, death, disenrollment, or 6‐month follow‐up. Inverse‐probability‐of‐treatment‐weighted (IPTW) cause‐specific hazards regression models were used to compare outcomes between patients who were new users of RAASi, amlodipine, or thiazides. Results: Our cohort included 16,504 antihypertensive users (RAASi, n = 9574; amlodipine, n = 5049; thiazide, n = 1881). Mean age was 83.5 years (± 8.2), 70.6% were female, and 17.2% were non‐white race. During a mean follow‐up of 5.3 months, 326 patients (2.0%) experienced an injurious fall, 1590 (9.6%) experienced MACE, and 2123 patients (12.9%) died. The intention‐to‐treat IPTW hazard ratio (HR) for injurious falls for amlodipine (vs RAASi) use was 0.85 (95% confidence interval (CI) 0.66–1.08) and for thiazides (vs RAASi) was 1.22 (95% CI 0.88–1.66). The rates of MACE were similar between those taking anti‐hypertensive medications. Thiazides were discontinued more often than other classes; however, inferences were largely unchanged in as‐treated analyses. Subgroup analyses were generally consistent. Conclusions: Older adults with limited life expectancy experience similar rates of injurious falls and short‐term cardiovascular events after initiating any of the first‐line antihypertensive medications. [ABSTRACT FROM AUTHOR]

The design of an experimental approach, the Box–Behnken design, was implemented to optimize the chromatographic condition to develop a rapid HPLC procedure for quantification of a ternary mixture of metoprolol (MET), telmisartan (TEL), and amlodipine (AML) from the formulation. The perturbation plots, contour, and 3D response surface pictures were developed to study the impact of each variable on the analytes' retention time and the probable interaction between the parameters with fewer chromatographic runs. The optimized HPLC method separated the three analytes within 5 min with excellent selectivity and peak shape on a Zorbax C18 HPLC column using acetonitrile and phosphate buffer (20 mM, pH 5.8) with isocratic elution at a 1.1 mL/min flowrate. A wavelength 230 nm was utilized to monitor the elute. The validation of proposed method demonstrated a wide linearity range of 10–200 µg/mL for MET and TEL and 5–50 µg/mL for AML along with an excellent correlation coefficient. The correctness of the HPLC approach was further confirmed by excellent recovery of the added amount of analytes utilizing the standard addition technique. The recommended HPLC approach was employed safely for quality assurance of the formulation, because the evaluation of the method's greenness and whiteness confirmed the environmentally friendly nature of the approach. [ABSTRACT FROM AUTHOR]

Background: Uncontrolled blood pressure is a major risk factor for cardiovascular diseases. Fixed-dose combination (FDC) therapy offers a promising approach to addressing this challenge by providing a convenient single-tablet solution that enhances the effectiveness of blood pressure control. In our systematic review, we assess the effectiveness of perindopril/amlodipine FDC in managing blood pressure. Methods: We conducted a comprehensive search across four primary electronic databases, namely, PubMed, Virtual Health Library (VHL), Global Health Library (GHL), and Google Scholar, as of 8 February 2022. Additionally, we performed a manual search to find relevant articles. The quality of the selected articles was evaluated using the Study Quality Assessment Tools (SQAT) checklist from the National Institute of Health and the ROB2 tool from Cochrane. Results: Our systematic review included 17 eligible articles. The findings show that the use of perindopril/amlodipine FDC significantly lowers blood pressure and enhances the quality of blood pressure control. Compared to the comparison group, the perindopril/amlodipine combination tablet resulted in a higher rate of blood pressure response and normalization. Importantly, perindopril/amlodipine FDC contributes to improved patient adherence with minimal side effects. However, studies conducted to date have not provided assessments of the cost-effectiveness of perindopril/amlodipine FDC. Conclusion: In summary, our analysis confirms the effectiveness of perindopril/amlodipine FDC in lowering blood pressure, with combination therapy outperforming monotherapy and placebo. Although mild adverse reactions were observed in a small subset of participants, cost-effectiveness assessments for this treatment remain lacking in the literature. [ABSTRACT FROM AUTHOR]

5-Fluorouracil is a chemotherapeutic agent used for the treatment of different kinds of cancers and Amlodipine Besylate is a vasodilator used to cure hypertension and angina. In order to improve different properties of drugs like drug solubility, mask bitter taste, prevent photodegradation, and for controlled drug delivery, the host–guest, solid inclusion complexes of 5-flurouracil (5-FU) and Amlodipine Besylate (ABS) with beta-cyclodextrin (β-CD) were utilized for different studies in this manuscript which were prepared through traditional methods and microwave-prompted technique. Different parameters such as apparent molar volume (Vϕ), partial molar volume at infinite dilution (Vϕ0), apparent molar isentropic compression (Kϕ,s), partial molar isentropic compression at infinite dilution (K0ϕ,s) were obtained from experimental density and speed of sound data. The partial molar volume at infinite dilution (Vϕ0 × 106/m3 mol−1) values of β-CD in aqueous solution of drug ABS was found 79.83, 80.32 and 80.64 at 305.15, 310.15 and 315.15 K, respectively. The partial molar volume at infinite dilution (Vϕ0 × 106/m3 mol−1) values of β-CD in aqueous solution of drug 5-FU was found − 252.61, − 246.42 and − 255.74 at 305.15, 310.15 and 315.15 K, respectively. The value of solubility constant (Ks) was found to be 74.3822 ± 4 M−1 for 5-FU and 204.0811 ± 4.75 M−1 for ABS in phase solubility studies. The inclusion complexes (ICs) were incorporated into the hybrid polymer networks (HPNs) of chitosan and gelatin to explore drug release studies. A comparison of directly loaded drug into the HPNs was made with the cyclodextrin-mediated release. The ICs prepared by different methods were also compared for the drug release. [ABSTRACT FROM AUTHOR]

Background: Calcium channel blockers, including the recently developed cilnidipine, are widely used as first-line medications for treating newly diagnosed cases of primary essential hypertension. Cilnidipine has a unique advantage compared to amlodipine, another common calcium channel blocker. While amlodipine only targets L-type calcium channels, cilnidipine can target both L and N-type channels. This study aimed to compare the effectiveness and safety of these two medications in patients with essential hypertension. Methods: A total of n=80 cases of mild to moderate hypertension were randomly allocated to two groups. Group I n=40 received a daily dose of Amlodipine 5mg, whereas those in Group II n=40 received Cilnidipine 10mg once daily, 30 minutes after breakfast, for 8 weeks. Participants were prohibited from using any other medications during the study period. Each patient underwent three visits: a baseline visit (Visit 0) on recruitment day, visit 1 after 30 days of medication, and Visit 2 after 60 days of treatment. Systolic and diastolic blood pressures, as well as heart rate, were measured at each visit. Clinical and laboratory parameters were reassessed at the end of the 8 weeks. Results: Both medications significantly reduced Systolic and Diastolic Blood Pressure (SBP and DBP) and heart rate in both groups over 8 weeks. While Group II (Cilnidipine) consistently showed slightly lower blood pressure and heart rate, these differences were statistically insignificant, suggesting similar effectiveness between the two medications in this study. Both groups reported mild/moderate adverse events, with Group I having a consistently higher number and wider range of events compared to Group II. The most common events were fatigue and headache, with Group I experiencing additional events like headache + GI upset, vomiting, and ankle edema. Conclusion: Both the calcium channel blockers amlodipine and cilnidipine exhibit equivalent efficacy in reducing systolic and diastolic blood pressure in patients with mild to moderate essential hypertension. Cilnidipine, as a fourth-generation calcium channel blocker, offers a promising pharmacological profile. In addition to its blood pressure-lowering effects, cilnidipine demonstrates notable safety and provides additional benefits including renoprotective, cardioprotective, and neuroprotective effects. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Practical Electrocardiology is the property of Journal of Practical Electrocardiology Editorial Board and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This research study aims to formulate, prepare and evaluate transdermal drug delivery system for the purpose of controlled release of Amlodipine Bebesylate as a model drug using different polymers as a rate controlling membraneamlodipine undergoes first pass metabolism and also has easy permeability through skin therefore transdermal system of Amlodipine Bebesylate can be developed. The transdermal patches for the delivery were prepared by evaporation method i.e., solvent evaporation method. A matrix-type amlodipine besylate transdermal drug delivery system was prepared using novel polymers such as hydroxypropyl methylcellulose (HPMC) and sodium carboxymethylcellulose (SCMC) and Carbopol P 934 as a rate controlling or rate limiting membrane which delivers the drug or releases the therapeutic drugin controlled and a predetermined manner and rate. The formula for the transdermal patch was optimized using the experimental design. On the basis of the Data from drug release studies and the drug content the optimized batch was found to be F14 showing 80.1% of drug release and 95.62% of drug content. The patches were also evaluated forvarious evaluation parameters such as thickness uniformity,weight variation, moisture content determination, hygroscopicity &tensile strength. [ABSTRACT FROM AUTHOR]

Thioureas and their derivatives are organosulfur compounds having excellent biological and non-biological applications. These compounds contain S- and N-, which are nucleophilic and allow for establishing inter-and intramolecular hydrogen bonding. These characteristics make thiourea moiety a very important chemosensor to detect various environmental pollutants. This article covers a broad range of thioureas and their derivatives that are used for highly sensitive, selective, and simple fluorimetric (turn-off and turn-on), and colorimetric chemosensors for the detection and determination of different types of anions, such as CN-, AcO-, F-, ClO- and citrate ions, etc., and neutral analytes such as ATP, DCP, and Amlodipine, etc., in biological, environmental, and agriculture samples. Further, the sensing performances of thioureas-based chemosensors have been compared and discussed, which could help the readers for the future design of organic fluorescent and colorimetric sensors to detect anions and neutral analytes. We hope this study will support the new thoughts to design highly efficient, selective, and sensitive chemosensors to detect different analytes in biological, environmental, and agricultural samples. [ABSTRACT FROM AUTHOR]

The suggested study adheres to a particular protocol to ensure that the process is environmentally friendly and sustainable. It is worth mentioning that several tools have been adopted as prospective measures of the method greenness. Fortunately, the established analytical method is identified as white by the white analytical chemistry (WAC) concept, which uses the red/ green/blue color scheme (RGB 12 tool) to combine ecological and functional factors for the first time in studying of the cited drug. Amlodipine (AMD), a cardiovascular treating agent, belongs to the dihydropyridine class of oral calcium channel‐blocking agents. This article presents a novel, simple, green, one‐pot‐processed, fast, and ultrasensitive fluorimetric approach for monitoring and assessment of AMD using molecular‐size‐dependent fluorescence augmentation of the light scattering‐driven signal of eosin, a biological stain at a wavelength of 415 nm. This enhancement was directly proportional to the size of the produced complex. The linearity range was from 30 to 900 ng mL−1, with corresponding sensitivity limits (detection and quantitation levels) of 9.2 and 28 ng mL−1, respectively. The planned approach was also successfully used to track AMD content in bulk, dosage forms, and bio‐fluids (human plasma and urine). The developed method's eco‐friendliness was established by different eco‐rating metric tools. [ABSTRACT FROM AUTHOR]

Symptoms of pancreatic cancer often present late, and most are non-specific and thus misinterpreted. Although a rare condition, the prognosis for pancreatic cancer is very poor, with a 5-year survival rate of 7.3%; however, this improves to 30% for early-stage diagnosis. Prediabetes or diabetes are found in around 80% of people diagnosed with pancreatic carcinoma and, importantly, are often identified a year or two ahead of this diagnosis. Thus, new-onset diabetes represents an opportunity for early detection of pancreatic carcinoma. Through this case report of an older gentleman with new-onset diabetes and a normal BMI, the authors discuss how healthcare professionals can identify people who might be at risk of pancreatic cancer, along with the differential diagnoses, and what actions they should take. [ABSTRACT FROM AUTHOR]

Objectives: The key objective of this work is to establish a stability-indicating UHPLC technique for measuring amlodipine and enalapril maleate in bulk and pharmaceutical formulations Materials and Methods: The mobile phase consisted of 0.02M KH2PO4 buffer: Methanol (70:30 v/v). The chromatographic separation was carried out using an Analytical Technologies UHPLC-3000 equipment in conjunction with a variable wavelength programmable UV identifier and a Rheodyne injector equipped with a 5 µL fixed circle. Detection was done at 224 nm with the flow rate of 0.3 mL/min. Results: Amlodipine's retention time was determined to be 0.7 min, while Enalapril's was 1.2 min. The linearity range for Amlodipine and Enalapril was discovered to be 5-25 µg/mL. The technique has been examined in accordance with ICH (International Conference on Harmonisation) standards. A procedure is precise and accurate if the %RSD is less than two. Amlodipine's limit of detection and quantitation ranges are 0.12-0.37 µg/mL and Enalapril's range is 0.10-0.30 µg/mL, respectively. The procedure proved to be simple, linear, swift, exact, accurate, repeatable, and reliable. The drug was prone to acid, basic, and oxidation conditions, according to the stress degradation research. Conclusion: Even in actual samples, the techniques clearly distinguished between the drugs and degradation products. The method was proved as a stability indicating method and can be used in practice for bulk and the dosage forms and also to evaluate the shelf life. [ABSTRACT FROM AUTHOR]

Copyright of UNIKA Journal of Health Sciences is the property of UNIKA Journal of Health Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Acute post-streptococcal glomerulonephritis (APSGN) is the most common glomerulonephritis of childhood, and clinical presentation can vary widely. This case report presents an atypical manifestation of APSGN in an 8-year-old female patient with pleuritic chest pain and elevated troponin-I, despite lacking classical kidney symptoms. Imaging studies showed cardiomegaly and interstitial lung opacities. Further investigations revealed hematuria and proteinuria, and the diagnosis was confirmed through elevated antistreptolysin-O (ASO) titers and low complement 3 (C3) levels. The patient was successfully managed with fluid restriction, diuretics, and antihypertensives, resulting in the resolution of symptoms and normalization of laboratory values. This case highlights the significance of recognizing atypical manifestations of APSGN for ensuring prompt diagnosis and proper management in the pediatric population. [ABSTRACT FROM AUTHOR]

The case report describes an 11-year old boy with sudden onset lower right limb thrombosis, hypertension and nephritic syndrome. Laboratory findings revealed positive results of anti-ANA, anti-dsDNA, lupus anticoagulant and COVID-19 IgG antibodies. Vascular ultrasound and computed tomography detected active thrombosis of the right popliteal vein. Kidney biopsy confirmed fourth class lupus nephritis. The patient responded well to a combination of steroids, cyclophosphamide, hydroxychloroquine, rituximab, alteplase, heparin and amlodipine, with the resolution of thrombosis and nephritic syndrome, stabilization of blood pressure and improvement in laboratory findings. The case highlights the importance of prompt diagnosis and appropriate treatment of systematic lupus erythematosus with vein thrombosis and lupus nephritis in children, particularly in male patients. Overall, this case emphasizes the possibility of virus triggering factors in systematic lupus erythematosus and the importance of regular check-ups, monitoring of symptoms in preventing complications and improving the long-term outlook for patients with systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]