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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]

• Methyldopa and amlodipine were the most frequently prescribed in the first trimester. • Nifedipine was the most frequently prescribed antihypertensive during pregnancy. • The MCM risk of first-trimester antihypertensives was not suggested. • The MCM risk of first-trimester amlodipine and methyldopa was not suggested. To evaluate the major congenital malformation (MCM) risk of first-trimester antihypertensive exposure, specifically of amlodipine and methyldopa. A large administrative claims database was used. The prevalence of antihypertensive prescriptions during pregnancy was described in 91,390 women giving birth between 2010 and 2019. The MCM risk of first-trimester antihypertensives was evaluated in 1,185 women diagnosed with hypertensive disorders in the first trimester. The MCM risk of first-trimester amlodipine and methyldopa was evaluated in 178 women who were prescribed antihypertensives in the first trimester. Antihypertensives were prescribed to 278 (0.30%) women during their first trimester. The prescription prevalence in the first trimester was highest for methyldopa (115, 0.13%), followed by amlodipine (55, 0.06%). Antihypertensives were prescribed to 2,955 (3.23%) women during pregnancy. Nifedipine (903, 0.99%) and nicardipine (758, 0.83%) were the most frequently prescribed oral and injectable antihypertensives during pregnancy, both with a significant increase in annual prevalence. Of the 1,185 women diagnosed with hypertensive disorders in the first trimester, antihypertensives were prescribed to 178 women. The adjusted odds ratio (aOR) of MCMs in the first-trimester prescription of any antihypertensive medication was 1.124 (95% confidence interval [CI], 0.618–2.045). Amlodipine and methyldopa were prescribed to 44 and 93 of the 178 women, respectively. The aORs of MCMs in the first-trimester prescription of amlodipine and methyldopa were 1.219 (95% CI, 0.400–3.721) and 0.921 (0.331–2.564), respectively. The MCM risk of first-trimester exposure to antihypertensives, including amlodipine and methyldopa, was not suggested. [ABSTRACT FROM AUTHOR]

[Display omitted] Burn wounds are a complicated process with ongoing psychological and physical issues for the affected individuals. Wound healing consists of multifactorial molecular mechanisms and interactions involving; inflammation, proliferation, angiogenesis, and matrix remodeling. Amlodipine (ADB), widely used in cardiovascular disorders, demonstrated antioxidant and anti-inflammatory effects in some non-cardiovascular studies. It was reported that amlodipine is capable of promoting the healing process by regulation of collagen production, extracellular matrix, re-epithelialization and wound healing through its vasodilation and angiogenic activity. The objective of the current study is to appraise the wound healing capacity of amlodipine-loaded SLN (ADB-SLN) integrated into a hydrogel. The in-vitro characterization revealed that the optimized formulation was nanometric (190.4 ± 1.6 nm) with sufficiently high entrapment efficiency (88 % ± 1.4) and sustained ADB release (85.45 ± 4.45 % after 12 h). Furthermore, in-vivo evaluation was conducted on second-degree burns induced in male Sprague-Dawley rats. ADB-SLN gel revealed a high wound contraction rate and a significant improvement in skin regeneration and inflammatory biomarkers levels, confirming its efficiency in enhancing wound healing compared to other tested and commercial formulations. To conclude, the present findings proved that ADB-SLN integrated hydrogel offers a promising novel therapy for burn wound healing with a maximum therapeutic value. [ABSTRACT FROM AUTHOR]

[Display omitted] • Room temperature synthesis and characterization of ZIF-8 MOF nanoparticles. • Fabrication of modified CPE by ZIF-8 MOF and silver ion. • Simultaneous quantification of amlodipine and clopidogrel by Ag@ZIF-8/CPE. • Advantages of stability, repeatability and reproducibility of the nanosensor. • Good capability of nanosensor for determination of AML and CLO in the human plasma. In this paper, we developed an electrochemical nanosensor for the measurement of the amlodipine (AML) and clopidogrel (CLO) drugs using the carbon paste electrode modified with ZIF-8 metal–organic framework (MOF) containing silver ions. It should be noted that the AML drug is used as an antihypertensive drug, and the CLO prevents blood platelets from sticking. Due to the consumption of AML and CLO drugs together, it is necessary to use accurate and reliable methods for the simultaneous measurement of AML and CLO in the pharmaceutical preparation and biological fluids such as human plasma with high accuracy and precision. So far, the simultaneous measurement of these drugs has not been performed using electrochemical methods. Firstly, characterization of the synthesized ZIF-8 MOF at room temperature was performed using various techniques. Based on N 2 sorption isotherms, the specific surface area, and average pore diameter of ZIF-8 were calculated to be 1626.2 m2/g and 32.3 nm, respectively. ZIF-8 MOF has unique features such as appropriate high surface area, pore volume, large pore size, and high porosity, which has made it widely used, especially in the field of electrochemistry. The modified carbon paste electrode (ZIF-8/CPE) was fabricated for the simultaneous measurement of AML and CLO drugs in the pharmaceutical and human plasma. The ZIF-8/CPE can adsorb more silver ion vs. bare CPE due to high surface area and porosity of ZIF-8, and can increase currents of AML and CLO electrooxidation. The optimum conditions for measurement of these drugs were obtained in terms of phosphate buffer (0.1 M, pH 3.0) and the applied potentials of 0.5 and 0.7 V before each measurement for AML and CLO, respectively in a period of 120 s. The values of diffusion coefficient were obtained to be 1.5 × 10-5 and 3.88 × 10-5 cm2 s−1 for AML and CLO, respectively. In addition, the catalytic rate constants were calculated to be 8.59 × 105 and 3.84 × 105 cm3 mol−1 s−1 for AML and CLO drugs, respectively. The limit of detection (LOD) values were calculated to be 50 and 10 nM, and the linear dynamic range (LDR) were achieved to be 0.16–200 and 0.03–250 µM for AML and CLO, respectively. Also, capability of the Ag@ZIF-8/CPE nanosensor was examined for determination of above drugs in the pharmaceutical and clinical samples via external calibration and standard addition methods. Recovery percentages were close to 100 for both drugs, indicating the selectivity and good performance of the Ag@ZIF-8/CPE nanosensor. [ABSTRACT FROM AUTHOR]

Background and Aims: To evaluate the long-term effect of simultaneous treatment of hypertension and hypercholesterolemia with angiotensin-converting enzyme (ACE) inhibitors and statins on the incidence of major cardiovascular events (MACE) and other clinical outcomes.Methods and Results: We considered data from a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. We excluded normotensive subjects and individuals with a low calculated 10-year CVD risk, hypertensive patients treated with antihypertensive drugs different from ACE inhibitors and patients who changed antihypertensive medications during follow-up. The remaining participants were divided into four groups depending on whether they were treated with (I) perindopril ± amlodipine without statin treatment (N. 132), (II) perindopril ± amlodipine and atorvastatin (N. 132), (III) an ACE inhibitor other than perindopril ± a calcium-channel blocker without statin therapy (N. 133), (IV) an ACE inhibitor other than perindopril ± a calcium-channel blocker and statin therapy (N. 145). The long-term (8 years) effects of the different combined treatment were compared among the pre-defined groups. Over the follow-up period of 8 years, the proportion of subjects who developed MACE, type 2 diabetes mellitus and hyperuricemia, and the proportion of subjects needing for the intensification of antihypertensive treatment to improve blood pressure control were statistically different among the predefined groups (P < 0.05).Conclusion: Combined treatment with ACE inhibitors and statins (especially atorvastatin) in hypertensive patients seems to significantly reduce the risk of developing CVD in comparison with treatment with ACE inhibitors alone. [ABSTRACT FROM AUTHOR]

Statins are the mainstay for the treatment of dyslipidemia. Recently, rosuvastatin has also been demonstrated to possess analgesic properties in animal studies. The present study has been planned to further confirm the analgesic activity of rosuvastatin, etoricoxib, tramadol, amlodipine, and amitriptyline and study the interaction of rosuvastatin with the above-mentioned analgesics. The objective of the study was to confirm the analgesic activity of rosuvastatin and determine the minimum analgesic dose of rosuvastatin, etoricoxib, tramadol, amlodipine and amitriptyline and to study the analgesic effect of combination of subanalgesic doses of rosuvastatin with sub-analgesic doses of etoricoxib, tramadol, amlodipine, and amitriptyline. After IAEC approval, the study was carried out in albino mice in two phases. In phase I, the analgesic effect of rosuvastatin, etoricoxib, tramadol, amlodipine, and amitriptyline was confirmed by using tail-flick and writhing methods. In phase II, analgesic effect of combinations of subanalgesic dose of rosuvastatin with subanalgesic dose of etoricoxib, tramadol, amlodipine, and amitriptyline was studied. Minimal analgesic dose of rosuvastatin, etoricoxib, tramadol, amlodipine, and amitriptyline was observed as 5, 20, 10, 5, and 10 mg/kg, respectively. In phase II, combination of subanalgesic dose of rosuvastatin 2.5 mg/kg with subanalgesic doses of etoricoxib (10 mg/kg), tramadol (5 mg/kg), amlodipine (2.5 mg/kg), and amitriptyline (5 mg/kg), demonstrated synergistic analgesic activity. Rosuvastatin exerts dose-dependent analgesic activity that is synergistic to that of etoricoxib, tramadol, amlodipine, and amitriptyline. If established in clinical studies as well, this finding can lead to the reduction of analgesic dosing in patients already on statins. [ABSTRACT FROM AUTHOR]

The adoption of biophotonic sensing technologies holds significant promise for application in health care and biomedical industries in all aspects of human life. Then, this piece of writing employs the powerful effective medium theory and FDTD simulation to anticipate the most favorable state and plasmonic attributes of a magnificent nanocomposite, comprising carboxylate functionalized carbon nanotubes and chitosan (CS). Furthermore, it thoroughly explores the exhibited surface plasmon resonance behaviors of this composite versus the quantity of CS variation. Subsequently, enlightening simulations are conducted on the nanocomposite with a delicate layer and a modified golden structure integrating as a composite. The intricate simulations eventually unveil an optimal combination to pave the way for crafting an exceptional specific biosensor that far surpasses its counterpart as a mere Au thin layer in terms of excellence. The proposed biosensor demonstrated linear behavior across a wide range from 0.01 μM to 150 μM and achieved a detection limit of 10 nM, with a sensitivity of 134◦RIU−1. [Display omitted] • Sensor chip modification with carboxylate functionalized carbon nanotubes (CCNT) and chitosan (CS) increased its sensitivity. • Carboxylate functionalized carbon nanotube- Chitosan thin film attracted Amlodipine causing refractive index change. • We emphasized to first optimize the desired composite with mathematical methods and then proceed to manufacture it. • The laboratory results were obtained in accordance with the simulation results. • We used real samples in testing the proposed sensor. [ABSTRACT FROM AUTHOR]

A miniature mass spectrometer (mMS) based point-of-care testing (POCT) method was evaluated for on-site detecting the hypertension drugs, amlodipine and benazepril. The instrument parameters, including voltage, ISO1, ISO2, and CID, were optimized, under which the target compounds could be well detected in MS2. When these two drugs were injected simultaneously, the mutual ionization inhibition and mutual reduction between amlodipine and benazepril were evaluated. This phenomenon was severe on the precursor ions but had a small impact on the product ions, thus making this POCT method suitable for analysis using product ions. Finally, the method was validated and applied. The blood samples from patients were tested one hour after oral administration of the drugs (20 mg), and the benazepril was quantitatively analyzed using a standard curve, with detected concentrations ranging from 190.6 to 210 μg L−1 and a relative standard deviation (RSD) of 8.6 %. In summary, amlodipine has low sensitivity and can only be detected at higher concentrations, while benazepril has high sensitivity, good linearity, and even meets semi-quantitative requirements. The research results of this study are of great clinical significance for monitoring blood drug concentrations during hypertension medication, predicting drug efficacy, and customizing individualized medication plans. [Display omitted] • A point-of-care testing method for hypertension drugs was established. • A miniature mass spectrometer was used for rapid on-site screening. • Amlodipine and benazepril in blood were on-site analyzed by POCT. • The POCT method was validated to be efficient and convenient. [ABSTRACT FROM AUTHOR]

[Display omitted] • Simultaneous analysis of five antihypertensive mixtures involving amlodipine and Angiotensin II receptor antagonists. • Utilization of Reflectance/Fluorescence modes for superior detection. • Fluorescence optimization to maximize signal intensity for each drug without quenching the other. • Single chromatographic system used for detection at two pH values. A novel and highly sensitive high-performance thin-layer chromatographic (HPTLC) method was developed and validated to quantify a combination of five pharmaceutical mixtures spiked to human plasma. The compounds comprised Amlodipine (AML) along with five angiotensin II receptor antagonist drugs (AIIRAs), namely Olmesartan (OLM), Telmisartan (TLM), Candesartan (CAN), Losartan (LOS), and Irbesartan (IRB). HPTLC was performed on silica gel 60 F254 plates using a mobile phase of Toluene: ethyl acetate: methanol: acetone: acetic acid (6:1.5:1:0.5:1, v/v/v/v/v). In a pioneering move, a reflectance/fluorescence detection mode was employed to identify two concurrently administered drugs at different pH levels for the first time. This method utilized the same chromatographic system, incorporating a specific measurement for AML at a neutral medium to achieve its maximum fluorescence at a 360 nm excitation wavelength, and measuring emission using a 540 nm optical filter. The process involved obtaining a very low fluorescence response from AIIRA. Subsequently, to enhance AIIRA's fluorescence, the plate was sprayed with perchloric acid to transition to a strong acidic medium, ultimately attaining the maximum fluorescence of AIIRA using various excitation wavelengths and a 400 nm emission filter. Through this strategic process, we could optimize the fluorescence signals of both drugs, thereby elevating the sensitivity of detection for this drug combination. AML demonstrated a linear range of 18–300 ng/band, while AIIRAs drugs exhibited a linear range of 6–150 ng/band. The method satisfied the International Conference on Harmonization (ICH) criteria for recovery, precision, repeatability, and robustness, showcasing exceptional sensitivity. The approach was successfully applied to quantify AML and AIIRAs drugs in both bulk drug and plasma samples, achieving high recovery percentages and minimal standard deviations. [ABSTRACT FROM AUTHOR]

Saw palmetto (SAW), the herbal drug used to treat prostatic hyperplasia, exerts its antiproliferative effects by blocking steroid 5 alpha-reductase (SRD5A1) activity, that has also been involved in gingival hyperplasia (GH) pathogenesis. Concurrently, folic acid (FA) could reduce GH prevalence via its antioxidant and anti-inflammatory effects. Thus, this study tended to assess the potential therapeutic efficacy of SAW, alone and along with FA, against amlodipine-induced gingival inflammation and overgrowth in rats. Rats were grouped into (CONT, AIGH, SAW, SAW-treated, FA-treated, and SAW + FA-treated). SAW and FA were administered once daily for 4 weeks. Gingival SRD5A1, CTGF, GSK-3β, and NLRP3 expressions, as well as T, DHT, MDA, TAC, ET-1, and MMP2 levels were determined. In addition, histopathological and immunohistochemical analyses of TNF-α, IL-6, TGF-β1, and α-SMA were documented. Results declared that SAW and FA administration markedly ameliorated amlodipine-associated GH and may be presenting a novel therapeutic avenue in the future. [Display omitted] • SAW inhibits SRD5A1 activity and, as a consequence, NF-κB activation • SAW and FA prohibits TNFα and IL-1β outflow, ET-1 synthesis, and MMP-2 release • SAW and FA suppresses GSK-3β-mediated activation of NLRP3 inflammasome • SAW and FA down-regulates TGF-β1 and α-SMA expression in the gingival tissue • SAW and FA counteracts amlodipine-induced gingival hyperplasia (AIGH) [ABSTRACT FROM AUTHOR]

[Display omitted] The objective of this research is to explore the impact of sinkers on the dissolution rate of tablets exhibiting coning in paddle dissolution tests. The ICH M9 guideline refers to the use of sinkers to mitigate coning issues. However, the effectiveness of sinkers on coning phenomena has not been comprehensively investigated. Therefore, this study evaluated whether applying sinkers of different shapes could alleviate coning problems. The dissolution profiles of amlodipine tablet formulations which had been clinically demonstrated to be bioequivalent were assessed in a USP2 Apparatus with and without sinkers. Moreover, the effects of artificially induced coning formed by adding cellulose particles of various sizes on dissolution profiles, and the impacts of sinkers on the dissolution delay caused by the cellulose particles were investigated. Our study suggested that the CLIPS sinker was effective in obtaining in vivo relevant dissolution profiles by facilitating the dispersion of coning. The effect of sinkers varied depending on their shapes and the characteristics of the particles that constituted the coning. These findings enhance our understanding of the effectiveness of sinkers in addressing coning issues and aid in predicting the in vivo dissolution performance of tablet formulations that exhibit coning during dissolution testing. [ABSTRACT FROM AUTHOR]

Background: SBP and DBP have important associations with cardiovascular events, but are seldom considered simultaneously.Objectives: This study sought to simultaneously analyze systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements on the associated risk of a primary composite outcome of all-cause mortality, myocardial infarction (MI), congestive heart failure (CHF), or stroke.Methods: This study analyzed ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) data, which randomized adults to chlorthalidone, amlodipine, or lisinopril. The authors evaluated the simultaneous association of repeated SBP and DBP measurements on the primary composite outcome, and each outcome using proportional hazards regression. The authors report hazard ratios using a "heat map" to represent high and low risk according to SBP and DBP combinations.Results: During a median follow-up of 4.4 years (interquartile range: 3.6-5.4 years), 33,357 participants experienced 2,636 MIs, 866 CHF events, 936 strokes, and 3,700 deaths; 8,138 patients (24.4%) had at least 1 event. For the composite outcome, all-cause mortality, MI, and CHF, a U-shaped association was observed with SBP and DBP, but the SBP and DBP associated with the lowest hazards differed for each outcome. For example, SBP/DBP of 140-155/70-80 mm Hg was associated with the lowest HR for all-cause mortality, compared with 110-120/85-90 mm Hg for MI and 125-135/70-75 mm Hg for CHF. In contrast, the association of SBP and stroke was linear.Conclusions: The risk pattern of SBP and DBP differs by clinical outcomes, and the SBP and DBP associated with the lowest risk. Our results suggest individualization of blood pressure targets may depend in part on the cardiovascular event for which the patient is most at risk. [ABSTRACT FROM AUTHOR]

In this research work, a heterogeneous photocatalytic process has been adopted for emergent pharmaceutical effluents treatment using amlodipine besylate as a contaminant molecule and Ag–TiO 2 as a nanocatalyst. The influence of amlodipine besylate initial solution pH and concentration, Ag doping content, catalyst mass, and contact time has been investigated. The obtained results indicate that Ag doping induces rutile-anatase phase transformation and improved the surface characteristics (higher surface area and larger average pore volume). The photodegradation of amlodipine besylate is very effective; the highest performance is found to be 100% for 1% doped TiO 2 nanocatalyst under optimum conditions (pH 6, 0.5 g L-1 catalyst content, 100 min). The experimental data of the photodegradation process are found to obey the Lagergren kinetic model. Besides, the overall reaction rate is most likely governed by the intra-particular mass diffusion of amlodipine besylate, regardless of the process experimental conditions. [ABSTRACT FROM AUTHOR]

Introduction: Amlodipine overdoses have significant cardiac toxicity and are difficult to treat. Methylene blue has potential as a treatment for overdoses.Methods: A randomized controlled study of methylene blue as a treatment for amlodipine toxicity was conducted in C57Bl/6 mice. A baseline echocardiography was followed by gavage administration of amlodipine (90 mg/kg). Five minutes after gavage, animals received either vehicle solution (controls) or methylene blue (20 mg/kg) by intra-peritoneal injection. Animals were continuously monitored, and cardiac parameters were acquired every 15 min up to two hours.Results: Only 50% of control animals survived to the two-hour endpoint compared to 83% that received methylene blue. Amlodipine delivery induced significant reduction in left ventricular ejection fraction (EF), fractional shortening (FS), stroke volume (SV), and cardiac output (CO) in the vehicle treated animals relative to animals in the treatment group (p < 0.05 vehicle versus Methylene blue for EF, FS, SV, CO, and HR).Discussion: The amlodipine dose induced cardiotoxicity that were effects were more pronounced in the untreated group. 50% vehicle controls quickly progressed into heart failure (within 90 min of exposure) and did not survive the two h observation endpoint. Distinctly, only one animal from the Methylene blue treatment group did not survive (83% survival) the study. Additionally, the surviving animals from the Methylene blue group displayed significantly higher ejection fraction, fractional shortening, stroke volume, and cardiac output compared to vehicle group, indicating that methylene blue preserved cardiac function.Conclusion: In this mouse model of amlodipine overdose, methylene blue decreased cardiac toxicity. [ABSTRACT FROM AUTHOR]

[Display omitted] • An efficient electrochemical sensor is developed for determination of AM, AT and AS simultaneously in real human serum. • The sensor has low LODs for AM, AT and AS, good reproducibility, stability, acceptable repeatability, and resistance to interference. • The sensor quantitatively measures AM, AT, and AS in human serum and pharmaceutical formulations with accepted recovery values. Concomitant administration of amlodipine (AM) and atorvastatin (AT) is a well-tolerated treatment and effective for blood and plaque inflammation in hypertensive patients with carotid atherosclerosis. In addition, a daily low dose of acetylsalicylic acid (AS) can protect patients suffering from cardiovascular diseases and recurrent acute ischemic stroke. In the present work we introduce a simple and efficient electrochemical sensor for determination of AM, AT and AS simultaneously in human serum samples. The sensor is fabricated by modifying the surface of glassy carbon electrode by two successive thin films from carbon nanotubes-ferrocene mixture (CNT-FC), and nickel chromium oxide nanoparticles (NiCr 2 O 4). Furthermore, the sensor is successfully used for detection of AM, AT and AS simultaneously in serum sample with changing their concentrations in the ranges (0.01 → 50 µM), (0.1 → 40 µM) and (0.01 → 30 µM), the detection limits are 0.95 nM, 0.87 nM and 1.26 nM, respectively. The sensor has a good catalytic capability due to synergism between its composite components: CNT, FC, and NiCr 2 O 4. The features of the sensor are large active surface area, good electrical conductivity, storage stability, reproducibility, and anti-interference capability. The sensor quantitatively measures the drugs in human serum and pharmaceutical formulations with accepted recovery values. [ABSTRACT FROM AUTHOR]

Accurate diagnosis and proper dosage determination of amlodipine are crucial due to the potential for severe side effects, including seizures, alterations in blood pressure, and changes in heart rate. Additionally, concurrent use of amlodipine with other medications can result in drug interactions, further elevating the risk of adverse effects. Our research demonstrates that the graphene oxide-chitosan (GO-CS) composite functioned as a modifier of the gold chip surface, leading to 0.75° angular changes in relation to the bare gold chip. We utilized the finite-difference time-domain method to verify the effectiveness of the SPR sensor and its damping field by determining the material's effective refractive index and optimizing it with effective medium theory. Our findings revealed that the GO-CS biosensor with sensitivity 249◦μM−1 has a linear range of 0.05–150 μM and a limit of detection (LOD) of 50 nM. Finally, we employed GO-CS/Au to identify this drug in common tablets and urine samples and compared the attained results with HPLC as a standard golden method, representing desirable features for real sample analysis. [Display omitted] • We emphasized to first optimize the desired composite with mathematical methods and then proceed to manufacture it. • The laboratory results were obtained in accordance with the simulation results. • We used real samples in testing the proposed sensor. [ABSTRACT FROM AUTHOR]

A simple schematic illustration the developed ADP-CPB electrostatic-coupled complex and fluorescence response augmentation based on MmRFS, a new spectroscopic strategy. [Display omitted] • The article presents a facile green method to analyze the amlodipine drug. • The method relies on a molecular-size-based complex as a fluorescent sensor. • The drug was determined in different matrices; a content uniformity test was applied. • The method is characterized by a short analysis time, low cost, and no extraction step. • The method was studied from a greenness viewpoint using various recent tools. This study introduces the first and unique Molecular-mass-Related Fluorescence Sensor as the first fluorimetric strategy for determining amlodipine. An environmentally friendly, single-step, and direct spectrofluorimetric approach was utilized to evaluate the analyte. In an acidic setting, combining the amlodipine medication and the fluorescent dye Cilefa Pink B generated an instantaneous ultra-fluorescent product. An increase in dye response after adding amlodipine was proportional to the molecular weight of the generated complex, as measured at 329 nm. was the idea of the applied fluorimetric analysis. The complexing process increased the molecular mass from 879.86 to 1288.739 g mol−1. The medication's range of 0.050–1.00 µg mL−1 is directly correlated with this molecular mass enlargement. The ideal settings for the changeable parameters of the system were established through an analysis of the response of the amlodipine-Cilefa Pink B system. Furthermore, the developed sensor complied with ICH (International Council for Harmonization) standards. The sensitivity limits were 0.0139 µg mL−1 (for the detection limit, LOD) and 0.042 µg mL−1 (for the quantification limit, LOQ). Additionally, this method effectively recovered the drug in its original and therapeutic dosage forms. Finally, the proposed process's environmental impact was also assessed through different modern greenness evaluation tools. [ABSTRACT FROM AUTHOR]

The therapeutic utility of the effective chemotherapeutic agent cisplatin is hampered by its nephrotoxic effect. We aimed from the current study to examine the possible protective effects of amlodipine through gamma-glutamyl transpeptidase (GGT) enzyme inhibition against cisplatin nephrotoxicity. Amlodipine (5 mg/kg, po) was administered to rats for 14 successive days. On the 10th day, nephrotoxicity was induced by a single dose of cisplatin (6.5 mg/kg, ip). On the last day, blood samples were collected for estimation of kidney function, while kidney samples were used for determination of GGT activity, oxidative stress, inflammatory, and apoptotic markers, along with histopathological evaluation. Amlodipine alleviated renal injury that was manifested by significantly diminished serum creatinine and blood urea nitrogen levels, compared to cisplatin group. Amlodipine inhibited GGT enzyme, which participates in the metabolism of extracellular glutathione (GSH) and platinum-GSH-conjugates to a reactive toxic thiol. Besides, amlodipine diminished mRNA expression of NADPH oxidase in the kidney, while enhanced the anti-oxidant defense by activating Nrf2/HO-1 signaling. Additionally, it showed marked anti-inflammatory response by reducing expressions of p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-κB), with subsequent down-regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1). Moreover, amlodipine reduced Bax/Bcl-2 ratio and elevated hepatocyte growth factor (HGF), thus favoring renal cell survival. Effective GGT inhibition by amlodipine associated with enhancement of anti-oxidant defense and suppression of inflammatory signaling and apoptosis support our suggestion that amlodipine could replace toxic GGT inhibitors in protection against cisplatin nephrotoxicity. [ABSTRACT FROM AUTHOR]

Objective Data: Chronic hypertension is associated with adverse perinatal outcomes, although the optimal treatment is unclear. The aim of this network metaanalysis was to simultaneously compare the efficacy and safety of antihypertensive agents in pregnant women with chronic hypertension.Study: Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov, and Google Scholar databases were searched systematically from inception to December 15, 2019. Both randomized controlled trials and cohort studies were held eligible if they reported the effects of antihypertensive agents on perinatal outcomes among women with chronic hypertension.Study Appraisal and Synthesis Methods: The primary outcomes were preeclampsia and small-for-gestational-age risk. A frequentist network metaanalytic random-effects model was fitted. The main analysis was based on randomized controlled trials. The credibility of evidence was assessed by taking into account within-study bias, across-studies bias, indirectness, imprecision, heterogeneity, and incoherence.Results: Twenty-two studies (14 randomized controlled trials and 8 cohorts) were included, comprising 4464 women. Pooling of randomized controlled trials indicated that no agent significantly affected the incidence of preeclampsia. Atenolol was associated with significantly higher risk of small-for-gestational age compared with placebo (odds ratio, 26.00; 95% confidence interval, 2.61-259.29) and is ranked as the worst treatment (P-score=.98). The incidence of severe hypertension was significantly lower when nifedipine (odds ratio, 0.27; 95% confidence interval, 0.14-0.55), methyldopa (odds ratio, 0.31; 95% confidence interval, 0.17-0.56), ketanserin (odds ratio, 0.29; 95% confidence interval, 0.09-0.90), and pindolol (odds ratio, 0.17; 95% confidence interval, 0.05-0.55) were administered compared with no drug intake. The highest probability scores were calculated for furosemide (P-score=.86), amlodipine (P-score=.82), and placebo (P-score=.82). The use of nifedipine and methyldopa were associated with significantly lower placental abruption rates (odds ratio, 0.29 [95% confidence interval, 0.15-0.58] and 0.23 [95% confidence interval, 0.11-0.46], respectively). No significant differences were estimated for cesarean delivery, perinatal death, preterm birth, and gestational age at delivery.Conclusion: Atenolol was associated with a significantly increased risk for small-for-gestational-age infants. The incidence of severe hypertension was significantly lower when nifedipine and methyldopa were administered, although preeclampsia risk was similar among antihypertensive agents. Future large-scale trials should provide guidance about the choice of antihypertensive treatment and the goal blood pressure during pregnancy. [ABSTRACT FROM AUTHOR]

A number of medical conditions are identified as risk factors for suicide death; in particular, cardiovascular illnesses are recognized as a major suicide risk factor. In this case, self-poisoning is the common method of suicide and cardiovascular drugs are among the major medications associated with fatal overdose, with calcium channel blockers being one of the most common agents. The present study describes two different fatal suicide cases involving four cardiovascular drugs: carvedilol, doxazosin and amlodipine (case 1) and diltiazem (case 2). The concentrations of the target cardiovascular drugs in the different biological specimens (central and femoral blood, urine, liver, brain) are presented, giving information about the potentially fatal data and the distribution of the drugs in the body. The study led to the implementation of a fast, sensitive and simple method for the detection and quantification of the four commonly prescribed cardiovascular drugs in post-mortem specimens including fluids and tissues for forensic purposes. The method was fully validated. The toxicological results of the studied cases are discussed, along with the autopsy results, histopathological evidence, and circumstances of death. The toxicological findings presented in the study provide new data regarding cardiovascular drugs in different post-mortem specimens, which will contribute to the currently limited knowledge about the toxicological profile of cardiovascular drugs and their distribution. • Two fatal suicide cases involving cardiovascular drugs are presented. • A fully validated LC-MS/MS method applied in postmortem specimens for cardiovascular drugs is described. • Information about distribution and potentially toxic to lethal concentrations of the drugs are given. • The toxicological findings provide new data regarding cardiovascular drugs in different post-mortem specimens, contributing to the currently limited knowledge. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two derivatization-free spectrofluorimetric methods were developed to assay atenolol and amlodipine for the first time. • The assay methods utilized both conventional and synchronous fluorescence spectroscopy for estimation of both compounds. • The methods were applied to assay the studied analytes in their pharmaceutical preparations. • The developed analytical methods were validated according to ICH guidelines. • The proposed methods could be applied in quality control laboratories. Fixed-dose combinations for treatment of hypertension are observed in many dosages in the global market because of their high efficacy compared to single component dosage forms. One of these effective combinations is atenolol/amlodipine which is usually administered to patients with hypertension. Hence, development of facile, accurate, and sensitive methods for simultaneous estimation of atenolol and amlodipine is of great importance for quality control testing and pharmacokinetic studies. In our study, we developed two spectrofluorimetric methods to estimate both compounds in different pharmaceuticals. The first method is based on the estimation of atenolol and amlodipine by double-scan conventional spectrofluorimetry where the fluorescence intensities of atenolol and amlodipine were measured at 299 and 434 nm after excitation at 274 and 358 nm, respectively. The second method depends on synchronous spectrofluorimetric measurements at Δλ = 70 nm, where atenolol is assayed at 266 nm and amlodipine is assayed at 363 nm. Methods' optimizations were carried out to select the optimum conditions that render high selectivity and sensitivity. Such optimizations included assessment of solvents, surfactants, buffer volumes and pHs. The conventional spectrofluorimetric method was rectilinear over concentration range of 30.0–300.0 ng mL−1 for atenolol and 0.25–7.00 µg mL−1 for amlodipine while the synchronous spectrofluorimetric method showed linearity over the ranges of 0.60–6.00 µg mL−1 for atenolol and 0.25–7.00 µg mL−1 for amlodipine with low detection limits (≤0.12 µg mL−1) for both compounds in the two methods. It is the first work that demonstrates estimation of atenolol and amlodipine in their combinations by conventional and synchronous spectrofluorimetry. Both methods were applied to estimate atenolol and amlodipine in different pharmaceuticals with high %recovery and low %RSD. [ABSTRACT FROM AUTHOR]

Hypertension and dyslipidemia significantly contribute to cardiovascular disease development. Their coexistence poses challenges in managing multiple medications, influencing treatment adherence. This study aimed to assess the efficacy and safety of a combined treatment approach using a fixed-dose combination therapy. This multicenter, 8-week, randomized, double-blind, Phase IV trial was named Telmisartan/Amlodipine/Rosuvastatin from Samjin Pharmaceuticals and evaluated the efficacy and safety of fixed-dose combination treatment in patients with essential hypertension and dyslipidemia. They were randomly assigned to 2 fixed-dose combination therapy groups, telmisartan 40 mg/amlodipine 5 mg/rosuvastatin 10 mg (TEL/ALD/RSV) or amlodipine 5 mg/atorvastatin 10 mg (ALD/ATV) after washout/run-in period. The primary outcomes were the change in mean sitting systolic blood pressure and the percentage change of LDL-C after 8 weeks of medical treatment. Adverse drug reactions and events were assessed. Of a total of 304 patients who underwent screening, 252 were randomized to the TEL/ALD/RSV group (125 patients) and the ALD/ATV group (127 patients). The mean (SD) ages of the TEL/ALD/RSV group and the ALD/ATV group were 67.4 (11.3) and 68.2 (10.6) years, respectively (P = 0.563). The least-squares mean (SE) in mean sitting systolic blood pressure changes between the 2 groups were –16.27 (0.93) mm Hg in the TEL/ALD/RSV group, –6.85 (0.92) mm Hg in the ALD/ATV group (LSM difference = –9.42 mm Hg; 95% CI, –11.99 to –6.84; P <.001). For LDL-C level changes, a significant difference was noted between the 2 groups: –50.03% (1.18%) in the TEL/ALD/RSV group, –39.60% (1.17%) in the ALD/ATV group (LSM difference = –10.43%; 95% CI, –13.70 to –7.16; P <.001). No severe adverse events were observed. TEL/ALD/RSV proved to be more efficient than ALD/ATV in lowering blood pressure and reducing LDL-C levels among patients with hypertension and dyslipidemia, with no notable safety concerns. (Curr Ther Res Clin Exp. 2024; XX:XXX–XXX). ClinicalTrials.gov identifier: NCT03860220. [ABSTRACT FROM AUTHOR]

Amlodipine (AML) is the initial therapy most commonly prescribed for patients with hypertension in China. However, AML monotherapy is often less effective in achieving blood pressure (BP) control than other agents. We performed a clinical study to evaluate efficacy and safety of a combination therapy with AML, olmesartan (OLM), or an OLM/hydrochlorothiazide (HCTZ) compound for Chinese patients with mild-to-moderate hypertension. In the clinical trial, patients were initially treated with OLM 20 mg/d combined with AML 5 mg/d. Then OLM was uptitrated to 40 mg/d or changed to an OLM/HCTZ (20/12.5 mg/d) compound if the patients did not reach the target of seated diastolic BP <90 mm Hg (<80 mm Hg in patients with diabetes) after 8 weeks. The overall response rate of the combination therapy was 59.2% (95% CI, 54.23%–63.97%) at Week 2 and gradually increased to 97.1% (95% CI, 94.93%–98.47%) at the end of the study (Week 16). The combination therapy with OLM or OLM/HCTZ was well tolerated. The total incidence of adverse events was 42.9% (n = 176). Most of the adverse events were mild in severity (39.5%; n = 162) and not associated with the drugs (33.2%). In conclusion, combination therapy with AML, OLM, or OLM/HCTZ can significantly lower BP safely and achieve a high BP control rate in patients with mild-to-moderate hypertension in China. ClinicalTrial.org identifier: ChiCTR-ONC-12001963. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the relationship between endogenous CYP3A markers and plasma amlodipine (AML) exposure and metabolism parameters in early postpartum and non-peripartum women.Methods: Twenty-four AML-treated early postpartum women with hypertensive disorders of pregnancy and 30 non-peripartum women with essential hypertension were enrolled. Blood samples for determination of CYP3A markers including total cholesterol-adjusted 4β-hydroxycholesterol (4β-OHC/TC), 25-hydroxyvitamin D (25-OHD), and AML and its metabolites in plasma were collected at 24 h after the AML treatment.Results: The plasma 4β-OHC/TC in postpartum women was higher than that in non-peripartum women, while the plasma 25-OHD was lower. The postpartum women had a lower plasma AML concentration and its metabolic ratio was higher. The plasma 4β-OHC/TC decreased as the number of days post-delivery increased. The plasma AML concentration increased as the number of days post-delivery increased, while the metabolic ratio of AML declined slightly. Tendency toward negative correlations between the plasma 4β-OHC/TC but not 25-OHD, and AML concentration were observed in both postpartum and non-peripartum women. In both groups, the plasma 4β-OHC/TC was correlated with the metabolic ratio of AML.Conclusions: The early postpartum women had higher plasma 4β-OHC and AML metabolism. The plasma 4β-OHC had positive relationships with amlodipine metabolism in both women groups. AML metabolism and plasma 4β-OHC may be useful as CYP3A markers in early postpartum and non-peripartum women. [ABSTRACT FROM AUTHOR]

A fast, sensitive and reliable green micellar liquid chromatographic method has been developed and validated for simultaneous determination of metoprolol (MET) and amlodipine (AMD). Separation was performed on X-Bridge ODS column (150 × 4.6 mm, 5 μm particle size) using a micellar mobile phase consisting of 100 mM sodium dodecyl sulfate, 20 mM sodium dihydrogen phosphate buffer pH 3.0 and 10% v/v n-butanol. The fluorescence detector was set at 275/ 303 nm (excitation/ emission) for MET and 364/ 455 nm (excitation/emission) for AMD. A linear response was obtained over the ranges of 0.1–10 μg/mL and 0.2–2 μg/mL for MET and AMD, respectively. The method reached limits of detection of 20 ng/mL for MET and 50 ng/mL for AMD. The proposed method was successfully employed for the determination of the two drugs in their combined pharmaceutical dosage form and in addition, it was extended for the determination of MET in spiked human plasma. Furthermore, the green character of the developed method was evaluated using the new tool "green analytical procedure index (GAPI)". The developed method was verified to be an excellent green method. • The first green micellar liquid chromatographic method for the determination of metoprolol and amlodipine. • The mobile phase is environment-friendly, containing a low percentage of organic modifier. • Separation of two drugs with different retention behavior without the need for gradient elution. • Metoprolol was determined in human plasma without tedious sample preparation. • Assessment of greenness of the proposed method using the analytical eco-scale and GAPI guidelines. [ABSTRACT FROM AUTHOR]

Abstract Hypertension increases the risk of heart disease and stroke, is commonly known as a silent killer disease and considered as one of the key risk factor for premature death and disability over the world. Herein, we report for the first time a sensitive, costless and reproducible voltammetric method for individual determination of five antihypertensive drugs namely, propranolol (PRO), timolol (TIM), amlodipine (AML), amiloride (AMI) and triamterene (TRI) using differential pulse voltammetry at bare/unmodified screen-printed carbon electrodes (SPEs) in presence of sodium dodecyl sulfate (SDS). Each drug exhibits an electrochemical signal in aqueous media which is significantly enhanced in presence of optimized concentration of SDS due to accumulation of the protonated drug molecules and electrostatically interaction with negatively charged micellar structures. As a result, the spherical micellar orientation of SDS onto the graphitic surface of SPEs offered the analytically sensitive determination of the target drugs over a wide linear concentration range with nano-molar detection limits possible negating the need for any complicated surface modifications. Finally, the proposed voltammetric method was successfully utilized in the individual determination of the target antihypertensive drugs in pharmaceutical formulations and human urine samples. Graphical abstract Electrochemical analyses of antihypertensive drugs (propranolol, timolol, amlodipine, amiloride and triamterene) were explored by employing unmodified screen-printed electrode (SPE) in micellar media. The SPE offered a costless, portable, sensitive, stable and reproducible sensor for detection of these drugs in pharmaceutical dosage and human fluid. fx1 Highlights • Voltammetric determination antihyperteinsive drugs using SPEs in presence of SDS was explored. • LOD was found to be 0.0056, 0.042, 0.18, 0.0107 and 0.006 µM for PRO, TIM, AMI, TRI and AML drugs, respectively. • SPEs utilized for determination of antihyperteinsive drugs in pharmaceutical and urine samples. [ABSTRACT FROM AUTHOR]

Abstract Surface energy is extensively adopted to predict the surface properties of materials nowadays. Our study was aimed at utilizing the surface free energy measured by inverse gas chromatography to determine inter-particle interactions and to describe the overall behaviour of mixtures. The model drugs of different solubility (tadalafil, levocetirizine dihydrochloride, vardenafil hydrochloride, and amlodipine besylate) and two grades of polyvinylpyrrolidone (Kollidon® 12 PF, Kollidon® VA 64) were mixed in various ratios. Investigated components were characterized using inverse gas chromatography, particle size distribution and specific surface area. We also determined the work of adhesion and cohesion between the components in the binary mixtures. Due to the formation of levocetirizine agglomerates, the effect of mixing time on both components of the surface free energy was also studied for the binary mixture with Kollidon® VA 64. The results based on the energy analysis, especially positive or negative excess surface energies in theoretical and real binary mixtures, indicate that we can predict whether the components can form the desired ordered (interactive) mixture. For this reason, we have proposed, to the best of our knowledge, different approach to predict the interactions between components and their behaviour in the binary mixtures using inverse gas chromatography in terms of the energy balance based only on the surface parameters (surface free energy, dispersive and specific surface energy). Therefore, the approach of energy balance is an innovative and comparatively simple tool for analysis and identification of interactions between components in particulate systems, which can also predict the quality of the mixing. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract Four new, simple, and reproducible spectrophotometric methods were developed and validated for the simultaneous determination of Amlodipine (AML) and Atorvastatin (AT) in bulk powder and pharmaceutical dosage form. The four methods include two progressive and two successive resolution techniques. The two progressive methods are Absorbance Subtraction (AS) and Amplitude Modulation (AM), while the two successive methods are Constant Value (CV) and Concentration Value. In the Concentration Value method, the concentration of the drugs is determined from the graphical representation without the use of regression equations. Linearity range for the two progressive methods was from 5 μg/mL–35 μg/mL while for the two successive methods was from 5 μg/mL–55 μg/mL. The four methods were validated according to the ICH guidelines and were found to be accurate, precise, and selective. The methods were also applied for determination of the mixture in the marketed pharmaceutical dosage form. Results obtained were compared with reported methods. Also, One-way ANOVA statistical test was done between all the proposed spectrophotometric methods where no significant differences were found. Graphical Abstract Unlabelled Image Highlights • The reported papers use multi-step methods. • Concentration Value can determine both drugs without regression equations. • Progressive methods can determine both drugs by one unified regression equation. • The good recovery and accuracy make them applicable in quality control laboratories. [ABSTRACT FROM AUTHOR]

Abstract Cyclodextrins (CDs) are cyclic oligosaccharides obtained from starch. They present a hydrophobic outer and a hydrophobic cavity and they can complex hydrophobic molecules. In addition to the conventional forms of CDs, there are its derivatives, which can bring characteristics relevant to the molecule. In this context the objective of this work was the modification of the β-cyclodextrin (β-CD) with hexanoic anhydride (β-CDM) and to perform the complexation of the drug amlodipine (AMLO) in β-CD or modified β-CD (β-CDM). The complexation occurred by suspension with subsequent lyophilization, by kneading and by simple physical mixture. The product of the modification was characterized by 1H NMR, HMBC and TGA being confirmed the esterification of the β-CD in hydroxyls C2 and C6. The complexes were analyzed by 1H NMR which indicated complexation by the presence of characteristic signals of the drug and of β-CD or β-CDM. In vitro drug release assays have shown that complex media with β-CDM had a faster release in aqueous media than dissolution of the drug in natural. This is interesting because amlodipine has a very prolonged action causing an accumulation of this substance in the organism. Graphical abstract Unlabelled Image Highlights • The cyclodextrin (CD) was modified to change its physicochemical properties. • Modification of the hydroxyl groups at C2 and C6 of the β-CD was carried out via esterification. • Evidences of the modification was given by the NMR-HMBC analyses. • The drug amlodipine was successfully encapsulated in β-CD or in β-CDM. • The release assay indicated a faster process using the complexed systems in aqueous medium than the drug itself. [ABSTRACT FROM AUTHOR]

Highlights • Reliable and easy-to-use LC–MS/MS-method for simultaneous determination of four antihypertensives (amlodipine, canrenone, hydrochlorothiazide, metoprolol) as standard practice for Therapeutic Drug Monitoring. • Use of stable isotope labeled analogues for each antihypertensive were obtained for internal standardization and quantitative analysis [2H 7 ]-MET, [13C 6 ]-AML, [2H 4 ]-CAN, [13C 6 ]-HCT. • LC–MS/MS-method serves as an effective tool to detect PK-alterations/nonadherence and helps to monitor antihypertensive pharmacotherapy in therapy-refractory arterial hypertension. • Investigation of pharmacokinetic parameters based on a compartmental modeling and a Bayesian fitting procedure. Abstract Background Therapy-refractory arterial hypertension is defined as a blood pressure (BP) in a subset of patients who fail to achieve BP control despite a three-drug regimen (including a diuretic). Various factors have impact on loss of therapy response. Drug-drug-interactions (DDIs) may cause altered pharmacokinetics (PK) of antihypertensive drugs. Upregulation of activity and expression of cytochrome P450 (CYP) enzymes can result in decreased plasma drug levels. Besides these PK considerations a significant problem could be nonadherence to drug therapy. In this regard Therapeutic Drug Monitoring (TDM) is a useful tool for detecting nonadherence. Therefore a LC–MS/MS-method for determination of Metoprolol (MET), Amlodipine (AML), Canrenone (CAN) and Hydrochlorothiazide (HCT) was developed. Methods An UHPLC-MS/MS method was developed and validated for simultaneous determination of MET, AML, CAN and HCT in plasma matrix. Extraction of serum samples consisted of simple protein precipitation using acetonitrile. Stable isotope labeled analogues for each antihypertensive were obtained for internal standardization and quantitative analysis ([2H 7 ]-MET, ([13C 6 ]-AML, [2H 4 ]-CAN, [13C 6 ]-HCT). Calibrators and quality controls were prepared in plasma matrix of normal individuals. Sample preparation: protein precipitation with acetonitrile and addition of internal standard-mix. Results All analytes were eluted within a runtime of 2.5 min. Linearity experiments were demonstrated in plasma over following concentration ranges: MET: 5–750 μg/l, AML: 1–50 μg/l, CAN: 10–500 μg/l, HCT: 5–500 μg/l (R2 > 0.993). Chromatographic separation was achieved using a C18 column (50 × 2.1 mm, 1.9 μm particle size) and an isocratic elution. LC–MS/MS analyses were performed on a triple quadrupole mass spectrometer using positive and negative electrospray ionization in selected reaction monitoring (SRM) mode. Ion transitions monitored for quantitation were m/z 268.2 → 74.1 for MET, m/z 409.1 → 238.0 for AML, m/z 341.2 → 91.0 for CAN and m/z 296.0 → 205.1 for HCT. For all analytes, inter- and intra-day precision (CV, %) varied between 1.7 and 14.0 and inter- and intra-day accuracy values ranged from −2.5 to 7.1%. The lower limits of detection and quantification were: 0.08 and 0.23; 0.05 and 0.15; 2.82 and 8.54; and 0.02 and 0.05 μg/l for MET, AML, CAN and HCT, respectively. Results of stability experiments were within the required range of +/− 15%. Conclusions Although the level of recommendation of TDM of antihypertensive drugs in patients with refractory hypertension is not yet established, the present LC–MS/MS-method can serve as an effective tool for detection of PK-alterations/nonadherence and may help to monitor antihypertensive pharmacotherapy. [ABSTRACT FROM AUTHOR]

Highlights • TiO 2 and Ag/TiO 2 nanoparticles were synthesized by sol-gel method. • Ag favors phase transformation of rutile into anatase and grain growth. • Photocatalytic performance was improved by 1% Ag content reaching 100% for 1 h and 40 min. • The optimum pH was found to be 6, acid medium, for maximum efficiency. Abstract A comparative study of the photocatalytic efficiency of pure and Ag doped TiO 2 on the enhanced performance for the degradation of pharmaceutical products (amlodipine besylate) in aqueous solution under UV irradiation, is presented. XRD analysis reveals that the presence of even small amount of 1% Ag favors rutile-to-anatase phase transformation and grain growth. The photodegradation of amlodipine besylate measurements indicate an optimum catalytic activity of catalyst 0.5 g/L to achieve an efficiency of 100% within 100 min at 10 mg/L concentration of pollutant. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • New unknown impurity was observed during the accelerated stability analysis in the tablets of amlodipine besylate. • UHPLC-MS and NMR techniques were employed to identify and to fully characterize this degradation compound. • The impurity is 3-ethyl 5-methyl 4-(2-chlorophenyl)-6-methyl-2-(morpholin-2-yl)-1,4-dihydropyridine-3,5-dicarboxylate. Abstract New unknown impurity at m/z 421.15 was observed during the accelerated stability analysis (40 °C/75% relative humidity) in the multi-component tablets of amlodipine besylate by reversed-phase ultra-high performance liquid chromatography–mass spectrometry (UHPLC–MS). UHPLC–MS and nuclear magnetic resonance (NMR) techniques were employed to identify and fully characterize the degradation compound. The degradation product was unambiguously identified as 3-ethyl 5-methyl 4-(2-chlorophenyl)-6-methyl-2-(morpholin-2-yl)-1,4-dihydropyridine-3,5-dicarboxylate and mechanism of its formation was proposed. It was confirmed that the degradation product was formed by the reaction of amlodipine with formaldehyde originating from the excipients present in the dosage form. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Amlodipine mucoadhesive film improved ocular permeation in presence of cyclodextrins. • SBCD improved permeation to the highest extent compared to other films. • Amlodipine-SBCD film could be effectively utilized for anti-inflammatory activity. • Binary and ternary molecular docking studies were performed to explain interactions. Abstract Mucoadhesive type ocular film has been prepared for studying the anti-inflammatory potential of amlodipine (AML) on carrageenan-induced rabbit model and the effect of sulphobutyl-ether-beta-cyclodextrin on corneal permeation was tested. Hydroxypropyl methylcellulose (HPMC) ocular film was prepared after complexation of amlodipine with β-cyclodextrin, (BCD), hydroxypropyl β-cyclodextrin (HPCD), and sulfobutylether β-cyclodextrin (SBCD). The film without cyclodextrin showed a maximum swelling, and erosion to the highest extent. Both drug release and permeation were highly diffusion controlled and highest improvement was observed with SBCD due to increased dissolution, compared to other formulations with or without cyclodextrin. Highest binding energy and highest extent of amorphization were noticed in the SBCD film formulation. Improved amlodipine release in-vitro and ocular permeation were found by the HPMC film formulation after complexation of the drug with cyclodextrins wherein SBCD exhibited both to the highest extent. Binary and ternary systems molecular docking studies confirmed the lowest energy of binding between amlodipine and BCD compared to HBCD and SBCD. Signs of acute inflammation were mitigated within 2 h of film application in the cul-de-sac. Presence of sulphobutyl-ether β-cyclodextrin in the amlodipine-HPMC film can improve ocular permeation significantly and could be utilized as mucoadhesive type formulation for anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effects of cinnamon on the pharmacodynamic (PD) & pharmacokinetic (PK) of amlodipine in hypertensive rats. The hypertensive control group of Wistar rats received L-NAME (40 mg/kg, daily, orally) only. The cinnamon group of rats was treated with cinnamon (200 mg/kg, daily, orally) along with L-NAME. Following 14 days treatment period, blood pressures of rats were monitored at designated intervals over 24 h utilizing a tail-cuff system for measuring blood pressure. To assess the oral PK; amlodipine was administered as a single oral dose of 1 mg/kg to rats and blood samples were collected at specified intervals over 24 h and analysed by UPLC-LC MS/MS. Synergistic decreased in rat's blood pressure was observed in presence of cinnamon + amlodipine. Simultaneous administration of cinnamon ameliorates the C max and AUC 0-t of amlodipine, the C max and AUC 0-t was 11.04 ± 1.01 ng/ml and 113.76 ± 5.62 ng h/ml for the cinnamon + amlodipine group as compared to 4.12 ± 0.49 ng/ml and 48.59 ± 4.28 ng h/ml for the amlodipine alone group. The study demonstrates that the use of cinnamon considerably decreases the blood pressure levels and enhances the PK parameters of amlodipine in hypertensive rats. [ABSTRACT FROM AUTHOR]

A rapid and sensitive method was established to determine amlodipine enantiomers using liquid chromatography-tandem mass spectrometry (LC–MS/MS). Stereoselective separation was performed on CHIRALCEL OZ-RH column (150 mm × 4.6 mm i.d., 5 μm) with acetonitrile-water (10 mM ammonium acetate, 0.5% ammonia solution) (95:5, v/v) at a flow rate of 0.5 mL/min. The substances were detected by mass spectrometer equipped with an electrospray ionization source interface in positive ion mode. Multiple reaction monitoring was selected with the transition of the m / z 409.1 → 238.0 for amlodipine enantiomers and m / z 237.0 → 194.1 for carbamazepine (IS) respectively. Calibration curves were linear at the range of 0.9375–120 ng/mL for both isomers with r >  0.99, while using a lower sample volume (50 μL) compared with previously reported enantiospecific methods The accuracy was at the range of 84.1–119.0% for R-amlodipine, and 87.4–118.2% for S-amlodipine, respectively. The within- and between-run precision (CV%) was within 10% in all cases for both enantiomers. Enantiomers were stable under different conditions, e.g. processed sample, short-term, residue, long-term and freeze/thaw. The LC–MS/MS method was successfully applied in pharmacokinetic study of amlodipine enantiomers in rats. It was observed the concentration of the S- amlodipine was significantly higher than that of the R-amlodipine in racemate-treated group. And there was no significant difference in the pharmacokinetic profiles of the S-amlodipine between the 10 mg/kg racemate- and 5 mg/kg S-amlodipine-treated groups. In addition, it was the first time to find that the main pharmacokinetic parameters (AUC (0-t) , AUC (0-∞) and C max ) of R-amlodipine were significantly lower in the 5 mg/kg R-amlodipine-treated group compared with the racemate-treated group. [ABSTRACT FROM AUTHOR]

Calcium (Ca 2+ ) plays an important role in angiogenesis, as it activates the cell migration machinery. Different proangiogenic factors have been demonstrated to induce transient Ca 2+ increases in endothelial cells. This has raised interest in the contribution of Ca 2+ channels to cell migration, and in a possible use of channel-blocking compounds in angiogenesis-related pathologies. We have investigated the ability of erythropoietin (Epo), a cytokine recently involved in angiogenesis, to induce Ca 2+ influx through different types of membrane channels in EA.hy926 endothelial cells. The voltage-dependent Ca 2+ channel antagonists amlodipine and diltiazem inhibited an Epo-triggered transient rise in intracellular Ca 2+ , similarly to a specific inhibitor (Pyr3) and a blocking antibody against the transient potential calcium channel 3 (TRPC3). Unlike diltiazem, amlodipine and the TRPC3 inhibitors prevented the stimulating action of Epo in cell migration and in vitro angiogenesis assays. Amlodipine was also able to inhibit an increase in endothelial cell migration induced by Epo in an inflammatory environment generated with TNF-α. These results support the participation of Ca 2+ entry through voltage-dependent and transient potential channels in Epo-driven endothelial cell migration, highlighting the antiangiogenic activity of amlodipine. [ABSTRACT FROM AUTHOR]

This paper describes a method for quantification of d -amphetamine and diphenhydramine in beagle dog plasma by organic solvent field-amplified sample stacking (FASS)-capillary zone electrophoresis (CZE), using amlodipine as the internal standard. The separation was carried out at 25 °C in a 40.2 cm × 75 μm fused-silica capillary with an applied voltage of 20 kV using 25 mM phosphate-18.75 mM borate (pH 3.5). The detection wavelength was 200 nm. Clean-up and preconcentration of plasma biosamples were developed by 96-well formatted liquid- liquid extraction (LLE). In this study, the peak areas of d -amphetamine, diphenhydramine and amlodipine in the plasma sample increased by the factor of 48, 67 and 43 compared to the CZE without sample stacking. The method was suitably validated with respect to stability, specificity, linearity, lower limit of quantitation, accuracy, precision and extraction recovery. The calibration graph was linear from 2 to 500 ng/ml for d -amphetamine and 2–5000 ng/ml for diphenhydramine. All the validation data were within the required limits. Compared with the LC/MS/MS method that we previously established, there was no significant difference between the two methods in validation characteristics, except the LLOQs. The developed method was successfully applied to the evaluation of pharmacokinetic study of the Quick-Acting Anti-Motion Capsules (QAAMC) in beagle dogs. [ABSTRACT FROM AUTHOR]

In this paper, a stable amorphous solid dispersion of an antihypertensive drug, amlodipine besylate (AMB) was prepared by entrapping it in a polymer matrix, polyvinyl pyrrollidone, in different weight ratios (AMB/PVP 05:95, 10:90, 20:80, 30:70). The glass forming ability of all binary dispersions were studied by means of differential scanning calorimetry and found good correlation between experimental T g and Fox Flory's prediction. By considering the daily dosage limit of 5 mg, a weight ratio of 05:95 was further considered for the study. The structures of neat and binary of AMB were characterized by density functional theory, Fourier transform infrared spectroscopy, Fourier transform Raman spectroscopy and UV–visible spectroscopy. Further, detailed molecular dynamics of both pure and binary were investigated using broadband dielectric spectroscopy to judge the physical stability of the amorphous dispersions. Translation-rotation coupling of AMB possibly explains the dual conductivity and dipolar nature of the secondary relaxation in neat AMB. Thus, the binary dispersion of AMB with commercially acceptable weight ratio with strong glass forming behaviour and better shelf life was prepared and characterized for practical applications. [ABSTRACT FROM AUTHOR]

Fixed dose combination (FDC) of valsartan (VAL) and hydrochlorothiazide (HCT) or VAL and amlodipine (AML) has been available in many countries for the treatment of hypertension. Due to drug-drug interaction potentials, in the current study we aimed to evaluate potent effects of HCT and AML on pharmacokinetics (PKs) of VAL when they are orally co-administered as FDC (VAL/HCT at 80/12.5 mg or 160/12.5 mg; and VAL/AML at 160/5 mg or 160/10 mg) products in healthy Korean subjects. Population pharmacokinetic (PK) modeling and analysis were performed by the nonlinear mixed-effects modeling software. PKs of VAL was described by two-compartment disposition model, first-order elimination, four-sequential first-order absorption model, correlation between apparent clearances and volumes of distribution, and lag time. For all FDCs, there were no statistically significant differences in both maximum concentration and areas under the concentration-time curves ( AUCs ) of VAL in comparison to those when administered VAL alone, except the combination of VAL/AML at 160/10 mg, where AUC 0–∞ increased by 11.8% in mean and 6.86% in median. In addition, there was an increasing trend in time to reach peak ( T max ) of VAL in FDCs, where it was increased by 0.22–0.34 h in mean and 0.40–0.44 h in median, except the combination of VAL/HCT at 160/12.5 mg. However, these differences in AUC 0–∞ and T max might not be considered as clinically important. In conclusion, HCT or AML has no potent effect on PKs of VAL when they are co-administered as FDC products. No dose adjustment for VAL is recommended when co-administered with HCT or AML. [ABSTRACT FROM AUTHOR]

Some common nanoparticles, such as Zinc Oxide have been used as nanocatalysts in many processes, but they also have an important application in water purification processes. In this research, ZnO based nanoparticles were used for the degradation of Amlodipine Besylate (AMB) and the effect of some main parameters, e.g. initial concentration of AMB, nanocatalysts dose, pH of the solution, temperature of the solution, H 2 O 2 dose, and the time of visible light irradiation, were investigated. The destruction amount was determined by UV-Vis spectroscopy. The synthesized nanoparticles were characterized by FE-SEM, XRD, FT-IR, BET, BJH, EDS, XRF and UV-Vis techniques. The maximum degradation of AMB was about 90% in 60 min of visible light irradiation with 100 μL of H 2 O 2 . [ABSTRACT FROM AUTHOR]

A sensitive and specific ultra-performance liquid chromatography tandem mass spectrometric (UPLC–MS/MS) method has been developed, validated and applied for the assay of Nebivolol and S-amlodipine in human plasma. Sample extraction was carried out through hybrid extraction method from 250 μL of human plasma sample. Linearity of the method was (r ≥ 0.9996) was found to be dynamic for both the analytes over concentration range of 25.0–4000 pg/mL. Chromatographic separation was achieved on UPLC column {Waters Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 micrometer)} with the mobile phase composition of 0.1% (v/v) formic acid in 5 mM Ammonium formate in water-acetonitrile (20:80, %v/v). Analytes Stability was assured under different requisite conditions in human plasma, reconstitution solution and diluents. Inter and intra-day assay precision and relative error (accuracy) were within ±5% for both analytes. The method was applied and reproduced to support a pharmacokinetic study of 5 mg Nebivolol (NEB) and 2.5 mg S-amlodipine (LAM) tablet on 9 healthy subjects. [ABSTRACT FROM AUTHOR]

A sensitive and specific method, utilising high performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS) was developed for the quantitative determination of amlodipine in dried blood spot (DBS) samples. Chromatographic separation was achieved using a Waters XBridge C18 column with gradient elution of a mixture of water and acetonitrile containing 0.1% formic acid (v/v). Amlodipine was quantified using a Waters Quattro Premier mass spectrometer coupled with an electro-spray ionization (ESI) source in positive ion mode. The MRM transitions of 408.9  m / z → 238.1 m / z and 408.9 → 294.0  m / z were used to quantify and qualify amlodipine, respectively. The method was validated across the concentration range of 0.5–30 ng/mL by assessing specificity, sensitivity, linearity, precision, accuracy, recovery and matrix effect according to the Food and Drug Administration (FDA) guidelines. This method was also validated clinically within a large pharmacoepidemiological study in which amlodipine blood concentration was determined in patients who had been prescribed this medication. [ABSTRACT FROM AUTHOR]

Background: Amlodipine is rarely used in the treatment of pregnant hypertensive women due to limited pharmacokinetic data during pregnancy and the postpartum period.Objective: To evaluate the pharmacokinetics of amlodipine besylate in the peri-partum period including quantities of placental passage, breast milk excretion and infant exposure.Study Design: This was a prospective study of pregnant women who were prescribed 5 mg of amlodipine daily for treatment of chronic hypertension and delivered at term. Cord and maternal blood samples were collected at delivery. On postpartum day 2, six paired maternal plasma and breast milk samples were obtained at 4, 6, 8, 12, 15 and 24 h following amlodipine dosing. Infant plasma samples were collected 24-48 h after delivery. All samples were analyzed for amlodipine concentration. A one compartment, first-order model was used to calculate pharmacokinetic estimates for maternal plasma.Results: Of the 16 patients enrolled in the study, 11 had cord blood and maternal serum collected at delivery, of which only 6 produced sufficient breast milk for sampling. Amlodipine was detected in infant cord blood plasma with a mean concentration of 0.49 ± 0.29 ng/mL compared to mean maternal serum level of 1.27 ± 0.84 ng/mL. Amlodipine concentrations in both in breast milk and infant plasma were undetectable at the lower limit of assay detection (<0.1 ng/mL). In the immediate postpartum period, the amlodipine elimination half-life was 13.7 ± 4.9 h, the area under the curve was 53.4 ± 19.8 ng*h/mL and the peak concentration was 2.0 ± 1.0 ng/mL.Conclusions: Amlodipine does cross the placenta in measurable quantities, but is not detected in breast milk or infant plasma at 24-48 h of life indicating that it is likely safe to use during the peripartum period. [ABSTRACT FROM AUTHOR]

A bilayer tablet, which consisted of telmisartan and amlodipine besylate, was formulated based on a Quality by Design (QbD) approach. The control and response factors were determined based on primary knowledge and the target values of the control tablet (Twynsta ® ). A D-optimal mixture design was used to obtain the optimal formulations in terms of D-mannitol, crospovidone, and MCC for the telmisartan layer, and CCM-Na, PVP K25, and Prosolv for the amlodipine layer. The quantitative effects of the different formulation factors on the response factors were accurately predicted using the equations of best fit and a strong linearity was observed between the predicted and actual values of the response factors. The optimized bilayer tablet was obtained using a numeric optimization technique and was characterized compared with a control (Twynsta ® ) by using various physical evaluations and in vivo pharmacokinetic parameters. The physical stability of Telmiduo ® was greater than that of Twynsta ® owing to the improvement of formulation factors. The in vivo pharmacokinetic parameters suggested that Telmiduo ® might have pharmaceutical equivalence and bioequivalence with Twynsta ® . Therefore, the bilayer tablet that consisted of telmisartan and amlodipine besylate could be produced using a more economical and simpler method than that used to produce Twynsta ® . Moreover, the suitability of QbD for effective product development in the pharmaceutical industry was shown. [ABSTRACT FROM AUTHOR]

A novel voltammetric sensor based on molecularly imprinted poly(aniline- co -anthranilic acid) for determination of amlodipine (AML) was developed. The sensor was prepared by electrocopolymerization of aniline and anthranilic acid in the presence of AML molecules and perchloric acid onto a glassy carbon electrode (GCE) using cyclic voltammetry (CV). Several parameters affecting the performance of the imprinted (MIP) and non-imprinted films (NIP) were optimized. Under optimized operational conditions, the proposed MIP/GCE sensor exhibits two distinct linear responses ranging from 0.01 nM to 0.08 nM and 0.3 nM to 8.0 nM respectively with a LOD (3σ/m) of 2.66 pM. The precision (RSD, n = 6) of the method for intra and inter-days was found to be 0.65% and 1.68% respectively. The selectivity of the MIP/GCE sensor against AML was investigated in the presence of various interfering molecules. The proposed sensor was successfully applied for the detection of AML in pharmaceuticals, human urine, human serum and plasma. The proposed MIP/GCE sensor appeared to be suitable for sensitive and precise quantification of AML in several matrices. [ABSTRACT FROM AUTHOR]

Liquid crystalline-molecularly imprinted polymer (LC-MIP) particles were first found to possess the floating behavior on the aqueous medium. Combined with molecular recognition, the LC-MIP was fabricated as a novel class of the controlled-release gastric retentive DDS. The LC-MIP was made using co-polymerization of methacrylic acid, 4-methyl phenyl dicyclohexyl ethylene (LC monomer with vinyl group), and ethylene glycol dimethacrylate with S -amlodipine ( S -AML) as model template drug. The optimum condition of the preparation of LC-MIP has been obtained relying on release behaviors of S -AML from the LC-MIP. The surface morphology of LC-MIP and three corresponding control samples, i.e., template-free LC-NIP, LC-free MIP, and LC-free NIP, were studied. Applying the LF model for the binding isotherm, imprinting factors was 2.80 for the LC-MIP with the crosslinking degree of 20.0%, whereas 6.70 for the LC-free MIP with high levels of crosslinker (80.0%). Furthermore, the phase transition behaviors of LC-based particles as well as drug-loaded LC elastomers were measured by a differential scanning calorimeter and the formed hydrogen bonding between S -AML and LC-MIP was demonstrated by FT-IR spectra. In vivo imaging experiment proved that the floating LC-MIP had significantly longer gastric residence time (>60 min) than the non-floating MIP reference (<30 min). In vivo pharmacokinetic study showed a plateau region between 1.5 and 22 h on the plasma concentration from the LC-MIP. In spite of lower imprinting factor, the relative bioavailability of the gastro-floating LC-MIP was 180.5%, whereas only 111.7% of the LC-free MIP. As a conclusion, the LC-MIPs indicated potentials for oral administration due to the innovative combination of floating and controlled release properties. [ABSTRACT FROM AUTHOR]