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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]

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]

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]

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]

Obstructive sleep apnea (OSA) and hypertension are common conditions that may be linked through sympathetic activation and water retention. We hypothesized that diuretics, which reduce the body water content, may be more effective than amlodipine, a blood pressure (BP)-lowering agent implicated with edema, in controlling OSA in patients with hypertension. We also aimed to compare the effects of these treatments on ambulatory blood pressure monitoring (ABPM). In a randomized, double-blind clinical trial, we compared the effects of chlorthalidone/amiloride 25/5 mg with amlodipine 10 mg on OSA measured by portable sleep monitor and BP measured by ABPM. The study included participants older than 40 who had moderate OSA (10–40 apneas/hour of sleep) and BP within the systolic range of 140–159 mmHg or diastolic range of 90–99 mmHg. The individuals in the experimental groups were comparable in age, gender, and other relevant characteristics. Neither the combination of diuretics nor amlodipine alone reduced the AHI after 8 weeks of treatment (AHI 26.3 with diuretics and 25.0 with amlodipine. P = 0.713). Both treatments significantly lowered office, 24-h, and nighttime ABP, but the two groups had no significant difference. Chlorthalidone associated with amiloride and amlodipine are ineffective in decreasing the frequency of sleep apnea episodes in patients with moderate OSA and hypertension. Both treatments have comparable effects in lowering both office and ambulatory blood pressure. The notion that treatments could offer benefits for both OSA and hypertension remains to be demonstrated. NCT01896661. • Obstructive sleep apnea (OSA) and hypertension may be linked through sympathetic activation and water retention. • Reduction of body water diuretics is not more effective than amlodipine in controlling OSA in patients with hypertension. • Diuretics and amlodipine have equivalent blood pressure-lowering effects in individuals with OSA and hypertension. [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]

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]

Abstract 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.

Hyunwook Ryu,1 Hyun Chul Kim,1 Inseung Jeon,1 In-Jin Jang,1 Joo-Youn Cho,1,2 Kyung Tae Kim,3 Jaeseong Oh1,4,5 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Addpharma, Inc., Yongin-si, Gyeonggi-do, Republic of Korea; 4Department of Pharmacology, Jeju National University College of Medicine, Jeju, Republic of Korea; 5Clinical Research Institute, Jeju National University Hospital, Jeju, Republic of KoreaCorrespondence: Jaeseong Oh, Department of Pharmacology, Jeju National University College of Medicine, Jeju, Republic of Korea, Email jaeseong5@jejunu.ac.krBackground: Management of hypertension and hyperlipidemia, which are common comorbid risk factors for cardiovascular diseases, require multiple medications. The development of a fixed-dose combination (FDC) containing ezetimibe, rosuvastatin, telmisartan, and amlodipine aims to enhance patient adherence and persistence, but the potential interactions among the four medications have not been studied. This study aimed to evaluate the pharmacokinetic (PK) interactions between the FDC of ezetimibe/rosuvastatin 10/20 mg (ER) and the FDC of telmisartan/amlodipine 80/5 mg (TA).Methods: An open-label, single-sequence, three-period, three-treatment crossover study was conducted in healthy male subjects. All subjects received ER for 7 days, TA for 9 days and ER combined with TA for 7 days during each treatment period. For PK analysis of total/free ezetimibe, rosuvastatin, telmisartan, and amlodipine, serial blood samples were collected for 24 hours at steady state. Safety profiles were assessed throughout the study.Results: Thirty-eight subjects were enrolled, and 34 subjects completed the study. The systemic exposure to each active ingredient after coadministration of the two FDCs was similar to that after each FDC alone. The geometric mean ratios and 90% confidence intervals for the maximum plasma concentration (μg/L) and the area under the plasma concentration-time curve (h·μg/L) of the combination therapy to monotherapy, assessed at steady state, were as follows: total ezetimibe, 1.0264 (0.8765– 1.2017) and 0.9359 (0.7847– 1.1163); free ezetimibe, 1.5713 (1.2821– 1.9257) and 0.9941 (0.8384– 1.1788); rosuvastatin, 2.1673 (1.7807– 2.6379) and 1.1714 (0.9992– 1.3733); telmisartan, 1.0745 (0.8139– 1.4186) and 1.1057 (0.8379– 1.4591); and amlodipine, 0.9421 (0.8764– 1.0126) and 0.9603 (0.8862– 1.0405). Both combination therapy and monotherapy were well tolerated by the subjects.Conclusion: The coadministration of ezetimibe/rosuvastatin 10/20 mg and ezetimibe/rosuvastatin 10/20 mg was well tolerated in healthy subjects, and the PK interaction between those two FDCs was not clinically significant.Keywords: drug‒drug interactions, pharmacokinetics, fixed-dose combination, ezetimibe, rosuvastatin, telmisartan, amlodipine

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. Materials 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. 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.

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]