Azilsartan Research Articles

A Systematic Literature Review and Network Meta-analysis of Azilsartan Medoxomil Compared to Other Anti-hypertensives Efficacy in Lowering Blood Pressure Amongst Mild to Moderate Hypertensive Patients.

A systematic literature review and network meta-analysis was conducted on azilsartan medoxomil (AZL-M) versus other antihypertensive drugs' efficacy in hypertensive patients. The search utilized English platforms, from January 2000 until December 2023, resulting in 10,380 articles being screened. Screening criteria included hypertension (mild or moderate); first-line treatment and washout periods; studies (monotherapy) with AZL-M, angiotensin type II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitor (ARNIs), beta-blockers, calcium channel blockers (CCBs), and diuretics, either as intervention or comparator; and antihypertension efficacy as an outcome measure. Study design was randomized clinical trials. Efficacy variables included absolute office systolic and diastolic blood pressure (BP) reductions. A total of 21 publications provided adequate data for analysis, of which 20 studies reported both systolic and diastolic BP and one study reported only the diastolic BP. In 21 studies on systolic BP, against the common comparator placebo, the differences in systolic BP were significantly in favor of AZL-M, amlodipine, candesartan, irbesartan, nebivolol, nifedipine, olmesartan, sacubitril valsartan, telmisartan, and valsartan. The surface under the cumulative ranking curve (SUCRA) ranking shows that AZL-M 80mg had the highest ranking, with a possibility of 93% being the best in all other included treatments. In 20 studies on diastolic BP, against the common comparator placebo, the differences in diastolic BP were significantly in favor of AZL-M, amlodipine, bisoprolol, nebivolol, olmesartan, sacubitril valsartan, telmisartan, and valsartan. The SUCRA ranking shows that AZL-M 80mg had the highest ranking, with a possibility of 90% being the best in all other included treatments. AZL-M at 40mg and 80mg shows favorable efficacy compared to other anti-hypertensives, and the 80mg dosage seemed to be the most efficacious of all the included treatments in reducing both office systolic and diastolic BP in patients with mild-to-moderate hypertension.

Azilsartan as a preventive agent against cyclophosphamide-induced testicular injury in male rats.

Cyclophosphamide (CP) is a popular cancer treatment; however, despite its efficacy, it is known to cause harm to the testicles. To mitigate the reproductive damage caused by CP in male rats, we examined the protective effect of azilsartan (AZ) on CP-induced testicular damage. Thirty Sprague-Dawley male rats were equally divided into three groups: normal control group: received 0.5% CMC suspension for 13 days; induction group: received a single dose of 200 mg/kg of CP on day 6 by intraperitoneal (IP) injection, azilsartan group: received azilsartan (4 mg/kg) orally for 5 days followed by a single dose of 200 mg/kg of (CP) on day 6 by IP injection, then azilsartan administered again for 7 days. Animals were sacrificed on day 14, and sperm characteristics, testosterone levels, and testicular histopathology were evaluated. Induction with CP caused a significant reduction in median value compared to normal control in sperm count (12.0 vs. 22.0 × 106/mm3), sperm motility (30 vs. 90%), abnormal sperm (30.32 vs. 14.43%), dead sperm count (32.43 vs. 10.49 × 106/mm3), DNA fragmentation (21.57 vs. 5.49%); meanwhile, azilsartan prevent these effects on median sperm count (17.0 × 106/mm3), sperm motility (70.0%), abnormal sperm (23.19%), dead sperm count (26.17 × 106/mm3), DNA fragmentation (13.81%), and improved plasmatic testosterone levels compared to the CP group and prevented histopathological alterations of the testes. Azilsartan's mitigation of CP's effects suggests it can prevent male rats' reproductive damage caused by CP. One possible explanation for AZ's protective effects is that it inhibits lipid peroxidation and has antioxidant properties.

Possibilities of Azilsartan Medoxomil for Preparation for Planned Percutaneous Coronary Intervention in Patients With Type 2 Diabetes Mellitus.

To evaluate the efficacy and safety of azilsartan medoxomil for preoperative preparation and improving the long-term prognosis of elective percutaneous coronary intervention (PCI) in patients with ischemic heart disease (IHD), arterial hypertension (AH), and type 2 diabetes mellitus (DM). The study sample included patients with type 2 DM referred for elective PCI who had poor blood pressure (BP) control according to 24-hour BP monitoring (24-BPM) (mean daily systolic BP ≥130 mmHg, mean daily diastolic BP ≥80 mmHg). The data were collected from 2018 through 2020. A total of 75 patients was included and distributed by simple randomization into two groups: group 1 (main, n=37) received azilsartan medoxomil as an antihypertensive drug at a dose of 40 mg/day (previously prescribed angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ARB) were discontinued); group 2 (control, n=38) continued on their previous antihypertensive therapy. The follow-up period was 6 months. During each of 5 consecutive follow-up visits, the patient was examined, 24-BPM was recorded, and urinary markers of renal dysfunction (glomerular filtration rate, GFR; neutrophil gelatinase-associated lipocalin, NGAL; urine albumin-creatinine ratio, UACR; kidney injury molecule, KIM-1; and interleukin-18, IL-18) were measured. During the azilsartan treatment, GFR decreased by 7.4%, while in the control group, it decreased by 18.9% (p<0.001). For 6 months of follow-up, no changes in the NGAL concentration were found in the main group, while the NGAL concentration in the control group increased by 12.9%. With azilsartan, there was a decrease in the urinary concentration of IL-18 (16.9%), while in patients of the control group, IL-18 increased (7.14%). Proteinuria progressed in both groups, which was expectable given the presence of DM; however, in patients receiving azilsartan, the UACR value increased by 37.5%, while in patients of the control group, it increased by 96.15%. These differences were statistically significant. No statistically significant differences were found in the concentrations of cystatin C and KIM-1. This study demonstrated two important facts: the possibility for diagnosing contrast-induced acute kidney injury (CI-AKI) using new, more sensitive markers of kidney damage, which is important for assessing the effectiveness of prevention, and the possibility of using ARBs, in particular azilsartan, for the prevention of CI-AKI in patients with IHD in combination with AH and DM.

Multifunctional polymeric nanofibrous scaffolds enriched with azilsartan medoxomil for enhanced wound healing.

A prolonged and compromised wound healing process poses a significant clinical challenge, necessitating innovative solutions. This research investigates the potential application of nanotechnology-based formulations, specifically nanofiber (NF) scaffolds, in addressing this issue. The study focuses on the development and characterization of multifunctional nanofibrous scaffolds (AZL-CS/PVA-NF) composed of azilsartan medoxomil (AZL) enriched chitosan/polyvinyl alcohol (CS/PVA) through electrospinning. The scaffolds underwent comprehensive characterization both in vitro and in vivo. The mean diameter and tensile strength of AZL-CS/PVA-NF were determined to be 240.42 ± 3.55nm and 18.05 ± 1.18MPa, respectively. A notable drug release rate of 93.86 ± 2.04%, was observed from AZL-CS/PVA-NF over 48h at pH 7.4. Moreover, AZL-CS/PVA-NF exhibited potent antimicrobial efficacy for Staphylococcus aureus and Pseudomonas aeruginosa. The expression levels of Akt and CD31 were significantly elevated, while Stat3 showed a decrease, indicating a heightened tissue regeneration rate with AZL-CS/PVA-NF compared to other treatment groups. In vivo ELISA findings revealed reduced inflammatory markers (IL-6, IL-1β, TNF-α) within treated skin tissue, implying a beneficial effect on injury repair. The comprehensive findings of the present endeavour underscore the superior wound healing activity of the developed AZL-CS/PVA-NF scaffolds in a Wistar rat full-thickness excision wound model. This indicates their potential as novel carriers for drugs and dressings in the field of wound care.

Changing Concepts About Optimal Target Blood Pressure and the Therapeutic Advantages of Azilsartan for Achieving it

The article discusses current issues of the treatment of arterial hypertension. According to presented data, so-called therapeutic nihilism is becoming one of the main barriers to achieving target blood pressure (BP). This nihilism is that despite evidence of the effectiveness of achieving lower BP values, practitioners do not intensify antihypertensive therapy sufficiently to achieve such values. The article specially addresses new criteria for the effectiveness of antihypertensive therapy, which reflect the therapy sustainability. The most commonly used indicator is the duration of the period, during which systolic BP remains in the therapeutic range. The prognostic significance of such indicators is discussed. In these conditions, it is very important to use the most effective antihypertensive drugs for initial antihypertensive therapy, including as a part of combination therapy. This tactic provides more frequent achievement of BP goals without the need for dose adjustment. In this regard, a systematic review was performed, which included sufficiently large randomized studies of the antihypertensive effectiveness of azilsartan medoxomil. This systematic review will provide comprehensive information on a possible role of using the angiotensin II receptor blocker azilsartan as a basic drug for the treatment of a wide range of patients with high BP. Most of the studies included in the systematic review assessed the effectiveness of combination therapy including azilsartan.

Quality-by-Design Optimization of Electrospinning Parameters to Formulate Scaffolds for Topical Inflammatory Disease Management <i>via</i> Drug Repurposing

This study investigates the fabrication of chitosan (CS)/polyvinyl alcohol (PVA) blend nanofibers via electrospinning, aiming to create nanofibers with enhanced properties for broad applications. The research focuses on optimizing electrospinning parameters to reduce bead formation and achieve uniform nanofiber morphology. A detailed experimental design, employing a nineteen-point plan developed with Design-Expert software, examined variables such as polymer concentration, distance from the needle to the collector, the required voltage, and the rate at which solution was ejected from the needle. Morphological characteristics of the nanofibers were analyzed using advanced microscopy, complemented by drug release and wound healing assessments. The optimal electrospinning conditions were determined to be a 1:3 CS/PVA solution concentration ratio, an 8 cm needle-to-collector distance, a 20 kV applied voltage, and a 1 mL/hour flow rate. Scanning electron microscopy revealed uniform nanofibers with diameters between 100 to 250 nm, devoid of bead defects. In-vitro analysis demonstrated a sustained release profile of azilsartan (AZL), while in-vivo studies on rats indicated enhanced wound healing, corroborated by histological examination. The findings suggest that CS/PVA nanofibers, fabricated under these conditions, possess promising characteristics for use as a drug-delivery scaffold in wound treatment applications.

APPROACH TO OPTIMIZE THE SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM FOR AZILSARTAN MEDOXOMIL USING BOX BEHNKEN DESIGN AND DESIRABILITY FUNCTION

Objective: Develop and optimize a novel self-micro emulsifying drug delivery system (SMEDDS) for enhancing the water solubility of Azilsartan (AZL) by employing the Box-Behnken design and the desirability function. Methods: The formulation of AZL-SMEDDS consists of clove oil (oil component), Tween 20 (surfactant), propylene glycol (co-surfactant) as the independent variables and the active drug. Using a 3-level Design, the impact of independent variables on the formulation was examined. These variables' specified ranges are 20-40 mg, 50-80 mg, and 5-30 mg for X1, X2 and X3 respectively. Particle size (Y1), PDI (Y2), and dissolution % (Y3) were the response variables investigated in this study. Results: The results indicated that the optimal values for Clove oil (X1), Tween 20 (X2), and Propylene glycol (X3) were determined to be 28.69, 76.45, and 24.93 (mg), respectively. Based on these optimized conditions, the predicted data points for the response variables Particle Size (Y1), Polydispersity (Y2), and dissolution % (Y3) were determined to be 59.85 nm, 0.729 and 55.406%, respectively. Conclusion: The empirical results obtained from the optimized formulation exhibited a strong correlation with the predicted values. The optimized AZL-SMEDDS formulation demonstrated a rapid rate of drug solubility and greater bioavailability than AZL powder.

Protective effects of Azilsartan against cyclophosphamide-induced ovarian toxicity in rats model.

Cyclophosphamide (CP) is an effective alkylating anticancer agent that is widely used in cancer chemotherapy, and it can cause ototoxicity and infertility in women. So, this study aimed to evaluate the protective effects of Azilsartan (AZ) as an antioxidant and anti-inflammatory agent in a rat model of CP-induced ovarian toxicity. After receiving the 28 female Wister rats, they were acclimatized in proper environmental conditions for a week and then randomly divided into four groups based on the study protocol. After 15days of the experiment, they were sacrificed, and organs were collected for biomarker detection (Using the ELISA technique) and histopathological analysis. The level of IL-10 was significantly (P<0.05) decreased in all treated groups compared to control hostile groups, while the TNF-α level was significantly (P<0.05) increased in AZ (220.67±7.88ng/mL) and AZ+CP groups (221.78±9.11ng/mL) compared to control negative/CP groups. Regarding the oxidative biomarker level, a significant increase was only found in the AZ+CP group (176.02±6.71nmol/mL) compared to the control negative group. On the other hand, histopathological findings revealed that ovarian sections in animals that received a single dose of CP had severe ovarian atrophy with significant follicular regression and deterioration, as well as depletion of stromal supportive tissues. Azilsartan drastically reduced CP-induced ovarian toxicity in vivo by enhancing oxidative stress and inhibiting inflammatory effects in ovarian cells.

Antihypertensive efficacy and safety of azilsartan medoxomil in patients with diabetes mellitus in real clinical practice. According to the CONSTANT study

Background. Obesity and associated diseases are the most common comorbidities in patients with arterial hypertension (AH). The combination of AH and type 2 diabetes mellitus (DM2) significantly exacerbates the cardiovascular risk in this patients. BP control is one of the key components of the multivariate approach to reducing the risk of DM 2 complications. The use of drugs with pronounced antihypertensive properties and at the same time the ability to improve metabolic parameters should be a priority in this category of patients. Assessing the efficacy and safety of azilsartan medoxomil, the last molecule from the ARB class in patients with AH and DM 2 is an urgent task.Purpose. Evaluation of antihypertensive efficacy and safety of azilsartan medoxomil in patients with AH and DM 2 and overweight or obesity.Materials and methods. 235 overweight or obese patients with AH and DM2 enrolled in the international multicenter observational non-interventional prospective study CONSTANT with azilsartan medoxomil according to the approved label. The observation period is 6 months.Results. The dynamics of SBP by visit 4 (6 months) was 29,7±14,5 mmHg, DBP - 13,36±10,9 mmHg (r≤0,001). Overall, the group achieved BP targets in 211 (89.41%) DM patients enrolled in the study. Response to therapy (reduction in SBP by at least 20 mmHg, DBP of 10 mm Hg) was obtained in 177 (75.0%) patients. Glycated hemoglobin (p&lt;0.001) and fasting glucose (p&lt;0.001) significantly decreased in patients with AH and DM. A decrease in total cholesterol, triglycerides, and LDL was observed, including in DM patients not taking statins (p&lt;0.001). Overall, a decrease in waist circumference was observed across the group (p&lt;0.005).Conclusion. Azilsartan medoxomil in real clinical practice proved to be a highly effective antihypertensive drug in patients with AH and DM. The ability of the drug, including in combination with other drugs, to improve the metabolic profile, reduce the volume of adipose tissue makes it a priority drug of choice in patients with AH, obesity and type 2 DM.

Efficacy and safety of azilsartan medoxomil in the treatment of hypertension: a systematic review and meta-analysis.

Angiotensin II receptor blockers (ARBs) are utilized for the management of hypertension and diabetes. Previous meta-analyses suggested that azilsartan medoxomil (AZL-M) improved blood pressure (BP) reduction, but there were no safety findings or suggestions for patients with hypertension or diabetes. We performed an efficacy and safety meta-analysis of randomized controlled trials (RCTs) evaluating AZL-M therapy for reducing BP in patients with hypertension. Patients with hypertension complicated by diabetes were analyzed. The relevant literature was searched in English and Chinese databases for RCTs involving AZL-M in hypertension. Efficacy variables included the change from baseline in the 24-h mean systolic/diastolic BP measured by ambulatory BP monitoring, the change from baseline in clinic systolic/diastolic BP, and responder rates. Safety variables included total adverse events (AEs), serious AEs, AEs leading to discontinuation, and AEs related to the study drug. The raw data from the included studies were utilized to calculate the odds ratio (OR) for dichotomous data and the mean difference (MD) for continuous data, accompanied by 95% confidence intervals (CIs). Statistical analysis was performed using R software. A total of 11 RCTs met the inclusion criteria, representing 7,608 patients, 5 of whom had diabetes. Pooled analysis suggested a reduction in BP among patients randomized to 40 mg of AZL-M vs. control therapy [24-h ambulatory blood pressure monitoring (ABPM) mean systolic blood pressure (SBP) (MD: -2.85 mmHg), clinic SBP (MD: -3.48 mmHg), and clinic diastolic blood pressure (DBP) (MD: -1.96 mmHg)] and for 80 mg of AZL-M vs. control therapy [24-h ABPM mean SBP (MD: -3.59 mmHg), 24-h ABPM mean DBP (MD: -2.62 mmHg), clinic SBP (MD: -4.42 mmHg), clinic DBP (MD: -3.09 mmHg), and responder rate (OR: 1.46)]. There was no difference in the reduction of risks, except for dizziness (OR: 1.56) in the 80-mg AZL-M group or urinary tract infection (OR: 1.82) in the 40-mg AZL-M group. Analysis of patients with diabetes revealed that AZL-M can provide superior management, while safety and tolerability were similar to those of control therapy. AZL-M appears to reduce BP to a greater extent than dose-control therapy and does not increase the risk of adverse events in patients with hypertension and diabetes compared with placebo. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=464284, identifier PROSPERO CRD42023464284.

Green Flow-gradient Micellar High Performance Liquid Chromatograpic method for Determination of a Hypertensive Combination ; Azilsartan Medoxomil and Chlorthalidone :Application to Spiked Human Plasma and Urine

Green Flow-gradient Micellar High Performance Liquid Chromatograpic method for Determination of a Hypertensive Combination ; Azilsartan Medoxomil and Chlorthalidone :Application to Spiked Human Plasma and Urine

Efficacy of azilsartan medoxomil in patients with hypertension and stable coronary artery disease in combination with type 2 diabetes

Aim. To study the effect of azilsartan medoxomil (AZL-M) on the 24-hour blood pressure (BP) profile in patients with hypertension (HTN), type 2 diabetes (T2D) and stable coronary artery disease (CAD).Material and methods. A total of 183 patients with CAD in combination with HTN and T2D took part in the study (100 men (54,64%), 83 women (45,36%)). All patients were previously prescribed a statin, antiplatelet therapy, a beta-blocker, and an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). At baseline, the proportion of people taking ARBs and ACEIs was 30% and 70%, respectively. All study participants were discontinued from a previously prescribed ARBs or ACE inhibitors and were prescribed 6-month AZL-M (Edarbi®) therapy. During this period, according to the study plan, patients visited the medical center to assess the effectiveness and safety of therapy and blood pressure changes.Results. The mean age of the patients was 65,0 years (60-69 years), while the mean body mass index (BMI) — 31,24 kg/m2. The mean age of female participants was higher than the mean age of males: 66,35±6,59 vs 62,72±8,82 years (p=0,002). The mean BMI in women was higher and was 33.08 kg/m2, while in men it was 30,74 kg/m2 (p=0,001). Six-month AZL-M therapy decreased 24-hour BP values. Thus, the time index of systolic blood pressure (SBP) hypertension in the daytime decreased from 63% to 12%, while at night from 70% to 10%, and the time index of diastolic blood pressure (DBP) hypertension in the daytime from 18% to 10%, and at night from 44% to 8%. The main result is confirmation of AZL-M effectiveness in relation to BP control, as well as good drug tolerability. At the visit after 1-month AZL-M therapy, target BP values were recorded in 45,4% of participants, and after six months — the proportion of people with normal 24-hour BP values was 69,9%.Conclusion. Edarbi® therapy in patients with HTN in combination with T2D and stable CAD leads to 24-hour BP normalization. At the same time, the drug has a good safety profile, since the reported adverse events were not related to the drug.

Antihypertensive efficacy and safety of azilsartan medoxomil in patients with CАD, obesity and metabolic disorders. According to the CONSTANT study

Background: epidemiological studies show that the most common arterial hypertension (AH) is complicated by coronary artery disease (CAD), such patients are classified as very high risk. Effective BP control in this category of patients is critical. Therefore, assessing the efficacy and safety of current antihypertensive drugs in patients with AH and CAD against obesity or overweight is an important task.Purpose. Evaluation of antihypertensive efficacy and safety of azilsartan medoxomil in patients with overweight or obesity and stable CAD.Materials and methods. 335 patients with stable CAD and overweight or obese enrolled in the international multicenter observational non-interventional prospective study CONSTANT with azilsartan medoxomil according to the approved label. The observation period is 6 months.Results. The dynamics of SBP by visit 4 (6 months) was 30,1±15,3 mmHg, DBP – 12,5±10,4 mmHg (r≤0,001). Overall, 84,5% of patients enrolled in the study achieved BP targets across the group. Response to therapy (reduction in SBP by at least 20 mm Hg, DBP of 10 mm Hg) was obtained in 75,2% of patients. In patients who did not take statins, the level of cholesterol, triglycerides and LDL decreased significantly (p&lt;0,001), the HDL did not change significantly. In patients with diabetes mellitus, a decrease in glycated hemoglobin was recorded (p&lt;0,001). Overall, a decrease in waist circumference was observed across the group (p&lt;0,005).Conclusion. Azilsartan medoxomil has high antihypertensive properties, the ability to influence the metabolic profile and volume of adipose tissue, as well as tolerability comparable to placebo, which makes it the drug of choice in patients with AH with CAD and obesity or overweight in real clinical practice.

Curative Effect of AD-MSCs against Cisplatin-Induced Hepatotoxicity in Rats is Potentiated by Azilsartan: Targeting Oxidative Stress, MAPK, and Apoptosis Signaling Pathways.

Despite its clinical value, cisplatin (CISP) is complicated by marked hepatotoxicity via inducing oxidative stress, inflammatory, and apoptotic pathways. This study aims to explore the protective impact of azilsartan (AZIL), an antihypertensive drug, in addition to adipose tissue-derived mesenchymal stem cells (AD-MSCs) on CISP-induced hepatotoxicity. After characterization and labeling of AD-MSCs by PKH26 dye, 54 Wistar male albino rats were randomly divided into nine groups: I (CONT), II (AZIL.H), III (CISP), IV (CISP + AZIL.L), V (CISP + AZIL.H), VI (CISP + AD-MSCs), VII (CISP + AZIL.L + AD-MSCs), VIII (CISP + AZIL.H + AD-MSCs), and IX (CISP + VITA C). Serum alanine aminotransferase (ALT), alanine aminotransferase (AST), and albumin levels were determined. Assessment of reactive oxygen species, malondialdehyde, and glutathione contents, and superoxide dismutase activity and histopathological evaluations were done on hepatic tissue. Quantitative real-time PCR was utilized to estimate the expression of TNF-α and IL-6 genes. Cell homing of labeled AD-MSCs to the liver tissues was investigated. Hepatic expression of JNK1/2, ERK1/2, p38, Bax, Bcl-2, and cleaved caspase-3 proteins was investigated by western blot analysis. CISP elevated serum ALT and AST activities, reduced albumin level, and remarkably changed the hepatic architecture. It increased the expression TNF-α and IL-6 genes, raised the expression of JNK1/2, ERK1/2, p38, Bax, and cleaved caspase-3 proteins, and diminished the Bcl-2 protein. By contrast, treatment of animals with either AZIL or AD-MSCs dramatically reduced the effects of CISP injection. Moreover, treatment with combination therapy (AZIL.L or H + AD-MSCs) considerably mitigated all previously mentioned alterations superior to AZIL or AD-MSCs alone, which might be attributed to the AZIL-enhanced homing ability of AD-MSCs into the injured liver tissue. In conclusion, the present findings demonstrated that AZIL improves the hepatoprotective potential of AD-MSCs against CISP-induced hepatotoxicity by modulating oxidative stress, mitogen-activated protein kinase, and apoptotic pathways.

Robust method operable design region for economical and eco‐friendly chromatographic analysis of azilsartan medoxomil and cilnidipine by incorporating a hybrid approach of green analytical chemistry and analytical quality by design

AbstractAccording to the concept of green analytical chemistry, the analytical method development should be carried out by avoiding or minimizing the usage of toxic organic solvents for the safety of human and aquatic animal life and the protection of the environment. Hence, the green analytical chemistry (GAC)‐assisted robust liquid chromatographic method has been developed for chromatographic analysis of azilsartan medoxomil and cilnidipine (CIL) using safe organic solvents. The chromatographic method was developed by the implementation of analytical quality by design using chemometrics and response surface modeling. The chromatographic separation was carried out using Shim‐Pack C18 (250 × 4.6 mm, 5.0 μm) column as stationary phase and ethanol: 0.1% V/V ammonia solution (45:55, %V/V) as mobile phase. The chromatographic peak of AZL and CIL was found to be at the retention time of 3.5 and 4.5 min, respectively. The flow rate was kept at 1.0 mL/min and the column oven temperature was set to 40˚C. The developed method was found to be validated as per the International Council for Harmonization Q2 (R1) guideline. The method was applied for the assay of fixed‐dose combination and results were found in compliance with the labeled claim. The greenness of the method was evaluated using GAC tools.

Implementation of White Analytical Chemistry-Assisted Analytical Quality by Design Approach to Green Liquid Chromatographic Method for Concomitant Analysis of Anti-Hypertensive Drugs in Human Plasma.

According to current concepts of white analytical chemistry (WAC), the use of organic solvents those are teratogenic and carcinogenic must be avoided for the protection of the environment and of the analysts. This led to the development and validation of the WAC-assisted green liquid chromatographic technique (reverse-phase high-pressure liquid chromatography (RP-HPLC)) for the simultaneous analysis of anti-hypertensive drugs (azilsartan medoxomil, chlorthalidone and cilnidipine) in human plasma and their fixed-dose combinations. The analytical quality by design approach was used in conjunction with the design of experiments and chemometrics concepts to develop the method. To develop the green RP-HPLC method, critical method variables (CMVs) and critical analytical attributes were identified using the multivariate analytical tools principal component analysis and partial least square regression. Using the Box-Behnken design, the design of experiments was used for CMV optimization and response surface analysis. It was possible to explore the analytical design space for the life cycle management of the RP-HPLC method. The developed method was found to be validated following International Council for Harmonization Q2 (R1) and M10 requirements. Using the red, green and blue paradigm, the existing and proposed chromatographic methods were evaluated for their validation efficacy, greenness profile and cost-effectiveness.

COMPARISON OF EFFICACY IN RENOPROTECTION BETWEEN AZILSARTAN AND ENALAPRIL: A RANDOMIZED CONTROLLED TRIAL

Background: Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) are reported to improve renal outcomes among patients with hypertension and chronic kidney disease (CKD), but there might be substantial differences in their renoprotective effects. Azilsartan medoxomil is a relatively new available ARB, highly specific angiotensin type 1 receptor and superior in terms of blood pressure reduction, with respect to other ARBs.&#x0D; Methods: The study employed a randomized controlled trial; hypertensive subjects with albuminuria &gt;30 mg/g creatinine at the outpatient clinic, Phramongkutklao Hospital, Bangkok, Thailand were randomly assigned to azilsartan 40-80 mg/day (n=27) or enalapril 10-40 mg/day (n=23) for 24 weeks. The primary outcome was the change in urine albumin creatinine ratio (UACR). UACR, estimated glomerular filtration rate (GFR), blood pressure and serum electrolytes were evaluated at baseline, 12 and 24 weeks.&#x0D; Results: A total of 50 patients with hypertension and albuminuria were recruited. At the end of treatment, systolic blood pressure level was significantly reduced in the azilsartan group compared with the enalapril group (-12.2 mmHg [95%CI -18.9 to -5.5] vs. -1.1 mmHg [95% -7.8 to 5.7], p=0.021). In addition, at 24 weeks, significantly reduced median UACR was observed in the azilsartan group compared with that of the enalapril group (-59.9 mg/g Cr [95% CI -284.6 to -31.0] vs. -40.4 mg/gCr [95% CI -129.4 to 88.3], p=0.026)). No statistically significant difference was found between the two groups in hyperkalemia, estimated GFR, acute kidney injury and serious adverse events.&#x0D; Conclusion: This study demonstrated that azilsartan had superior antihypertensive and albuminuric efficacy compared with the standard dose of enalapril without increasing adverse events.

Azilsartan Ameliorates Skeletal Muscle Wasting in High Fat Diet (HFD)-induced Sarcopenic Obesity in Rats via Activating Akt Signalling Pathway

An association between the loss of skeletal muscle mass and obesity in the geriatric population has been identified as a disease known as sarcopenic obesity. Therefore, therapeutic/preventive interventions are needed to ameliorate sarcopenia. The present study investigates the effect of azilsartan (AZL) on skeletal muscle loss in High-Fat Diet (HFD)-induced sarcopenic obese (SO) rats. Four- and fourteen-months male Sprague Dawley rats were used and randomized in control and azilsartan treatment. 14 months animals were fed with HFD for four months and labeled as HFD-fed SO rats. Young & old rats received 0.5% carboxymethyl cellulose as a vehicle/AZL (8 mg/kg, per oral) treatment for six weeks. Grip strength and body composition analysis were performed after the last dose of AZL. Serum and gastrocnemius (GN)muscles were collected after animal sacrifice. AZL treatment significantly increased lean muscle mass, grip strength, myofibrillar protein, and antioxidant (superoxide dismutase & nitric oxide) levels in SO rats. AZL also restored the muscle biomarkers (creatine kinase, myostatin & testosterone), and insulin levels. AZL improves cellular, and ultracellular muscle structure and prevents type I to type II myofiber transitions in SO rats. Further, immunohistochemistry results showed increased expressions of pAkt and reduced expression of MuRF-1 and TNF-α exhibiting that AZL intervention could decrease protein degradation in SO rats. In conclusion, present results showed that AZL significantly increased lean mass, and restored muscle biomarkers, and muscle architecture. Taken together, the aforementioned findings suggest that azilsartan could be a possible therapeutic approach to reduce muscle wasting in sarcopenic obesity.

Second-Order Derivative Spectrophotometric Method for Simultaneous Estimation of Azilsartan Medoxomil and Cilnidipine in Combined Dosage Form

Second-Order Derivative Spectrophotometric Method for Simultaneous Estimation of Azilsartan Medoxomil and Cilnidipine in Combined Dosage Form

ВАЗОПРОТЕКТИВНЫЕ ВОЗМОЖНОСТИ КОМБИНАЦИЙ СОВРЕМЕННЫХ АНТИГИПЕРТЕНЗИВНЫХ ПРЕПАРАТОВ У ПАЦИЕНТОВ С АРТЕРИАЛЬНОЙ ГИПЕРТОНИЕЙ, САХАРНЫМ ДИАБЕТОМ 2 ТИПА И НЕАЛКОГОЛЬНОЙ ЖИРОВОЙ БОЛЕЗНЬЮ ПЕЧЕНИ

The aim of the study was to compare the effectiveness of the effect of combinations of azilsartan medoxomil (Az-M) with amlodipine (Aml) and olmesartan medoxomil (Ol-M) with Aml on achieving target blood pressure levels (CPP), parameters of vascular wall stiffness and central aortic pressure (CAP) in patients with arterial hypertension (AH), combined with type 2 diabetes mellitus (DM2) and non-alcoholic fatty liver disease (NAFLD). Materials and methods: 137 patients with uncontrolled hypertension combined with DM2 and NAFLD were examined. Patients were randomized into 2 groups: group 1 (n=68) was assigned a combination of Az-M with Aml at an initial dosage of 40/5 mg/day, in group 2 (n=69) patients received a fixed combination of Ol-M/Aml 20/5 mg/day. In addition to the general clinical examination, initially, after 4, 8, 12 and 24 weeks, they measured office blood pressure. Determination of the parameters of vascular wall stiffness and CAP was performed initially and after 24 weeks of the study. Taking into account the persons who did not reach the blood pressure target and dropped out of the study after 12 weeks, the evaluation of the studied parameters was carried out in 59 and 58 patients for groups 1 and 2, respectively. Results: the study demonstrated high antihypertensive efficacy of both combinations of antihypertensive drugs: the frequency of achievement of blood pressure control by patients of the 1st and 2nd groups after 12 weeks of treatment was 86.8% and 84.1% of cases, respectively. However, a more pronounced vasoprotective efficacy was characteristic of the combination of Az-M with Aml: in the 1st group of patients, there was a more pronounced positive dynamics of vascular wall stiffness and CAP.