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European Review For Medical and... Dec 2013To investigate the effects of Olmesartan Medoxomil (OM) on left ventricle hypertrophy (LVH) and inflammatory cytokines IL-6 and IL-10 levels in renovascular hypertensive...
AIM
To investigate the effects of Olmesartan Medoxomil (OM) on left ventricle hypertrophy (LVH) and inflammatory cytokines IL-6 and IL-10 levels in renovascular hypertensive rats.
MATERIALS AND METHODS
Qualified 30 male Wistar rats were randomly divided into three groups: sham-operation group (SO, n=10), model control group (MC, n=10), and Olmesartan Medoxomil group (OM, n=10). Renovascular hypertension was induced by ligating the abdominal aorta and 10 mg/kg OM was administered daily to the OM group by gastric perfusion for 7 weeks. The ratio of left ventricle mass to body weight (LVM/BW) was calculated as the index of cardiac hypertrophy, and the inflammatory cytokines IL-6 and IL-10 in serum and cardiac tissue were measured by ELISA assays.
RESULTS
The LVM/BW ratios in the MC group were about 50% higher than that in the SO group (p < 0.001). The OM group showed much reduced LVM/BW ratios compared with the MC group (p < 0.001) and were similar to that in the SO group (p > 0.05), indicating a complete reversal of the left ventricular hypertrophy caused by aorta ligation. The IL-6 and IL-10 levels in both the serum and cardiac tissue increased following aorta ligation (MC vs. SO, p < 0.001). While OM treatment significantly reduced IL-6 levels in the aorta-ligated rats (OM vs. MC, p < 0.001), IL-10 levels were not affected (OM vs. MC, p > 0.05).
CONCLUSIONS
OM completely reversed left ventricle hypertrophy and reduced IL-6 levels in renovascular hypertensive rats. Its effect on IL-10 levels in this animal model was not statistically significant.
Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Biomarkers; Disease Models, Animal; Down-Regulation; Hypertension, Renovascular; Hypertrophy, Left Ventricular; Imidazoles; Inflammation Mediators; Interleukin-6; Male; Olmesartan Medoxomil; Rats; Rats, Wistar; Tetrazoles; Ultrasonography; Ventricular Remodeling
PubMed: 24379062
DOI: No ID Found -
Hypertension Research : Official... Apr 2004Although angiotensin II receptor blockers (ARBs) have been recommended as a first line of anti-hypertensive agents in patients with diabetes, it remains unclear whether...
Although angiotensin II receptor blockers (ARBs) have been recommended as a first line of anti-hypertensive agents in patients with diabetes, it remains unclear whether ARBs have a favorable effect on insulin action and triglyceride (TG) metabolism, both of which are impaired in type 2 diabetes. In this study we addressed this issue by investigating how a newly developed ARB, olmesartan medoxomil, influenced insulin sensitivity and TG metabolism in fructose-fed rats, a representative animal model of insulin resistance. Olmesartan was administrated as a 0.01% drinking solution ad libitum to rats either fed normal chow or fructose-enriched chow (60%) for 21 days. Olmesartan treatment markedly decreased both systolic and diastolic blood pressure in both chow-fed and fructose-fed animals. The area under the curve of insulin (AUCI) was substantially greater in fructose-fed rats in the intravenous glucose tolerance test, and olmesartan treatment significantly reduced the AUCI. Olmesartan significantly improved the insulin sensitivity index in fructose-fed rats assessed by Bergman's minimal model without affecting insulin-independent glucose disposal. Olmesartan significantly decreased plasma TG and non-esterified fatty acid levels in fructose-fed rats without affecting lipoprotein lipase mass. The TG secretion rate determined by the triton WR1339 technique was two-fold higher in fructose-fed rats, but olmesartan restored the TG secretion to a normal rate. Olmesartan did not affect plasma parameters, insulin sensitivity or TG metabolism in chow-fed rats. Olmesartan ameliorates insulin resistance and overproduction of TG in fructose-fed rats, and these effects appear to be independent of its hypotensive action.
Topics: Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Blood Glucose; Blood Pressure; Fatty Acids, Nonesterified; Fructose; Glucose Tolerance Test; Heart Rate; Imidazoles; Insulin; Insulin Resistance; Lipoprotein Lipase; Male; Olmesartan Medoxomil; Rats; Rats, Wistar; Tetrazoles; Triglycerides
PubMed: 15127887
DOI: 10.1291/hypres.27.293 -
Indian Journal of Pharmaceutical... Sep 2009Two UV Spectrophotometric and one reverse phase high performance liquid chromatography methods have been developed for the simultaneous estimation of amlodipine besilate...
Two UV Spectrophotometric and one reverse phase high performance liquid chromatography methods have been developed for the simultaneous estimation of amlodipine besilate and olmesartan medoxomil in tablet dosage form. First UV spectrophotometric method was a determination using the simultaneous equation method at 237.5 nm and 255.5 nm over the concentration range 10-50 mug/ml and 10-50 mug/ml, for amlodipine besilate and olmesartan medoxomil with accuracy 100.09%, and 100.22% respectively. Second UV spectrophotometric method was a determination using the area under curve method at 242.5-232.5 nm and 260.5-250.5 nm over the concentration range of 10-50 mug/ml and 10-50 mug/ml, for amlodipine besilate and olmesartan medoxomil with accuracy 100.10%, and 100.48%, respectively. In reverse phase high performance liquid chromatography analysis carried out using 0.05M potassuim dihydrogen phosphate buffer:acetonitrile (50:50 v/v) as the mobile phase and Kromasil C18 (4.6 mm i.d.x250 mm) column as the stationery phase with detection wavelength of 238 nm. Flow rate was 1.0 ml/min. Retention time for amlodipine besilate and olmesartan medoxomil were 3.69 and 5.36 min, respectively. Linearity was obtained in the concentration range of 4-20 mug/ml and 10-50 mug/ml for amlodipine besilate and olmesartan medoxomil, respectively. Proposed methods can be used for the estimation of amlodipine besilate and olmesartan medoxomil in tablet dosage form provided all the validation parameters are met.
PubMed: 20502580
DOI: 10.4103/0250-474X.58190 -
Journal of Analytical Methods in... 2017A study was carried out to investigate compatibility of amlodipine besylate and olmesartan medoxomil with a variety of pharmaceutical excipients. Both drugs are...
Development and Validation of a Chromatography Method Using Tandem UV/Charged Aerosol Detector for Simultaneous Determination of Amlodipine Besylate and Olmesartan Medoxomil: Application to Drug-Excipient Compatibility Study.
A study was carried out to investigate compatibility of amlodipine besylate and olmesartan medoxomil with a variety of pharmaceutical excipients. Both drugs are antihypertensive agents that can be administered alone, in monotherapy, or in pharmaceutical association. The studies were performed using binary and ternary mixtures, and samples were stored for 3 and 6 months at 40°C under 75% relative humidity and dry conditions. For this study, a method based on high-performance liquid chromatography (HPLC) was developed and validated for the simultaneous determination of amlodipine besylate and olmesartan medoxomil in samples from pharmaceutical preformulation studies using diode array detector (DAD) and charged aerosol detector (CAD). The runtime per sample was 10 min with retention time of 7.926 min and 4.408 min for amlodipine and olmesartan, respectively. The validation was performed according to ICH guidelines. The calibration curve presents linear dynamic range from 12 to 250 g mL for amlodipine and from 25 to 500 g mL for olmesartan with coefficient of determination ( ≥ 0.9908) while repeatability and reproducibility (expressed as relative standard deviation) were lower than 1.0%. The excipients such as corn starch, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, talc, polyvinylpyrrolidone, lactose monohydrate, and polyethylene glycol showed potential incompatibilities after accelerated stability testing.
PubMed: 29391967
DOI: 10.1155/2017/4878316 -
Electrolyte & Blood Pressure : E & BP Dec 2023As combination therapy, switching to single-pill combination (SPC) medication after a short period of monotherapy is helpful because reducing pill numbers can improve...
The Efficacy of Single-pill Combination of Olmesartan Medoxomil and Amlodipine Besylate on Office Blood Pressure in Hypertensive Patients who did not Respond to Amlodipine Besylate Monotherapy.
BACKGROUND
As combination therapy, switching to single-pill combination (SPC) medication after a short period of monotherapy is helpful because reducing pill numbers can improve patients' adherence to medications. This study was aimed to assess the effect of the single-pill combination (SPC) of olmesartan medoxomil 20 mg and amlodipine besylate 5mg (OLM 20 mg/AML 5 mg) on blood pressure (BP) reduction in hypertensive patients who did not respond to amlodipine besylate 5 mg (AML 5 mg) monotherapy for 4 weeks.
METHODS
This study was a prospective, open-label, multi-center, non-comparative study. Patients whose BP was not got the target BP (≥140 mmHg and if diabetic patients ≥130 mmHg) after 4 weeks treatment with AML 5 mg, were enrolled. AML 5 mg was switched to the SPC (OLM 20 mg/AML 5 mg) treatment for 8 weeks. The primary effectiveness endpoint was the reduction of seated systolic blood pressure (SeSBP) after SPC (OLM 20 mg/AML 5 mg) treatment for 8 weeks. The changes of brachial-ankle pulse wave velocity (baPWV), central BP (CBP), and augmentation index (AIx@75) were evaluated also.
RESULTS
Forty-seven patients were enrolled (mean age = 52±9 years, 36 men). After the SPC treatment for 8 weeks, SeSBP was reduced from 153±9 mmHg to 131±18 mmHg and seated diastolic BP (SeDBP) from 95±8 mmHg to 81±11 mmHg (p<0.001 and p<0.001, respectively). The reduction of SeSBP/SeDBP were 22 mmHg and 14 mmHg, respectively. The target goal BP achievement rate was 74.5%, and baPWV, CBP, and AIx@75 were improved.
CONCLUSION
SPC (OLM 20 mg/AML 5 mg) treatment for 8 weeks was effective in reducing BP, achieving target BP goal, and also improving arterial stiffness in uncontrolled hypertensive patients with AML 5 mg monotherapy.
PubMed: 38152599
DOI: 10.5049/EBP.2023.21.2.45 -
Vascular Health and Risk Management Sep 2010Angiotensin receptor blockers have emerged as a first-line therapy in the management of hypertension and hypertension-related comorbidities. Since national and... (Review)
Review
Angiotensin receptor blockers have emerged as a first-line therapy in the management of hypertension and hypertension-related comorbidities. Since national and international guidelines have stressed the need to control blood pressure to <140/90 mmHg in uncomplicated hypertension and <130/80 mmHg in those with associated comorbidities such as diabetes or chronic kidney disease, these goal blood pressures can only be achieved through combination therapy. Of several drugs that can be effectively combined to attain the recommended blood pressure goals, fixed-dose combinations of angiotensin receptor blockers and the calcium channel blocker amlodipine provide additive antihypertensive effects associated with a safe profile and increased adherence to therapy. In this article, we review the evidence regarding the beneficial effects of renin-angiotensin system blockade with olmesartan medoxomil and amlodipine in terms of blood pressure control and improvement of vascular function and target organ damage.
Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Blood Vessels; Drug Therapy, Combination; Humans; Hypertension; Imidazoles; Tetrazoles
PubMed: 20859541
DOI: 10.2147/vhrm.s6663 -
International Journal of Nanomedicine 2019The intention of this work was to load olmesartan medoxomil (OLM), a sparsely water soluble antihypertensive bioactive with low oral bioavailability (26%), into...
INTRODUCTION
The intention of this work was to load olmesartan medoxomil (OLM), a sparsely water soluble antihypertensive bioactive with low oral bioavailability (26%), into PEGylated bilosomes (PBs) for augmenting its transdermal delivery. PBs contain PEGylated single chain edge activator besides the components of traditional bilosomes (Span 60, cholesterol and bile salts). The PEG gives further resilience to vesicle membrane and is speculated to augment both permeability and bioavailability of OLM.
METHODS
A 2 factorial experiment was constructed to inspect the impact of diverse variables on vesicles' features and sort out the optimal formula adopting Design Expert software utilizing thin film hydration technique. Vesicles' evaluation was done by finding out entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and amount of drug released after 6 hrs (Q6h). The optimal formula was selected and characterized for further investigations.
RESULTS
The optimal formula (PB15) showed spherical vesicles with EE% of 72.49±0.38%, PS of 559.30±10.70 nm, PDI of 0.57±0.15, ZP of -38.35±0.65 mV and Q6h of 59.60±0.24%. PB15 showed higher deformability index (28.39±5.71 g) compared to traditional bilosomes (5.88±0.90 g) and transethosomes (14.94±0.63 g). Further, PB15 showed superior skin permeation from rat's skin relative to the drug suspension. Moreover, confocal laser scanning microscopy examination revealed efficient penetration of the fluoro-labeled PB15 through skin. Histopathological study ensured the safety of PB15. In addition, in-vivo skin deposition studies showed higher OLM deposition in rat's skin from PB15 compared to transethosomes and OLM suspension. Furthermore, pharmacodynamic and pharmacokinetic studies performed using male Wistar rats and male Albino rabbits, respectively, showed the superiority of PB15 over oral tablets. PB15 was found to have significantly higher AUC and AUC relative to the oral tablets. As well, the relative bioavailability of PB15 was found to be 235.04%.
CONCLUSION
Overall, the obtained results confirmed the creditable effect of PB15 for transdermal delivery.
Topics: Administration, Cutaneous; Administration, Oral; Animals; Antihypertensive Agents; Bile Acids and Salts; Biological Availability; Calorimetry, Differential Scanning; Drug Delivery Systems; Male; Olmesartan Medoxomil; Particle Size; Permeability; Polyethylene Glycols; Rabbits; Rats, Wistar; Skin; Skin Absorption; Tablets
PubMed: 31616143
DOI: 10.2147/IJN.S213613 -
Core Evidence 2016Azilsartan (AZI) is a relatively new angiotensin receptor blocker available for the treatment of any stage of hypertension, which was eventually given in combination... (Review)
Review
BACKGROUND
Azilsartan (AZI) is a relatively new angiotensin receptor blocker available for the treatment of any stage of hypertension, which was eventually given in combination with chlorthalidone (CLT).
OBJECTIVE
To review pharmacology and clinical role of AZI monotherapy and AZI/CLT or AZI/amlodipine combination therapies for hypertension management.
METHODS
PubMed, Embase, and Cochrane Library were searched using search terms " azilsartan", "chlorthalidone," "pharmacology," "pharmacokinetics," "pharmacodynamics," "pharmacoeconomics," and "cost-effectiveness." To obtain other relevant information, US Food and Drug Association as well as manufacturer prescribing information were also reviewed.
RESULTS
Randomized controlled trials demonstrated AZI to be superior to other sartans, such as valsartan, olmesartan, and candesartan, in terms of 24-hour ambulatory blood pressure monitoring (ABPM) reduction with respect. That beneficial effect of azilsartan was also associated with similar safety profiles. When compared to other antihypertensive drugs, azilsartan was found to be superior to any angiotensin-converting enzyme inhibitor, including ramipril, in terms of ABPM results, and noninferior to amlodipine in terms of sleep-BP control. The association of AZI and CLT was then found to be superior to other sartans + thiazide combination therapies in terms of both BP lowering and goal achievement. The combination of AZI and amlodipine has also been tested in clinical trials, but compared only with placebo, demonstrating its superiority in terms of efficacy and similarity in terms of safety.
CONCLUSION
Azilsartan is a safe and effective treatment option for every stage of hypertension, both alone or in fixed-dose combination tablets with chlorthalidone or amlodipine. Beneficial effects of AZI were also noted in patients with any degree of renal impairment. In addition, safety profiles of AZI were similar to that of the placebo.
PubMed: 27103882
DOI: 10.2147/CE.S81776 -
Circulation Reports Sep 2020Angiotensin II receptor blockers (ARBs) are widely used for the management of hypertension in Japan; however, comparative efficacy data within the ARB drug class remain...
Angiotensin II receptor blockers (ARBs) are widely used for the management of hypertension in Japan; however, comparative efficacy data within the ARB drug class remain limited. This systematic literature review identified randomized controlled trials (RCT) indexed in PubMed and Ichushi in Japanese patients with hypertension receiving ARB monotherapy (azilsartan, candesartan cilexetil, irbesartan, losartan potassium, olmesartan medoxomil, telmisartan, valsartan) in at least 1 arm. Of 763 RCTs identified, 77 met the eligibility criteria; of which, 37 reported mean change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline in the office setting and were used to construct the network. A fixed-effects model (FEM) showed the effect of each drug vs. the reference, azilsartan. Using the FEM, the mean (95% credible interval) change from baseline in SBP/DBP for candesartan cilexetil, irbesartan, losartan potassium, olmesartan medoxomil, telmisartan, and valsartan was 3.8 (2.9-4.8)/2.6 (2.0-3.1), 4.8 (2.0-7.5)/3.7 (1.8-5.6), 3.0 (0.8-5.1)/1.9 (0.5-3.3), 3.2 (1.2-5.1)/2.7 (1.3-4.1), 3.2 (0.8-5.6)/2.0 (0.3-3.6), and 3.1 (1.1-5.1)/2.4 (1.1-3.8) mmHg, respectively. The results of this meta-analysis provide evidence that azilsartan has a more favorable efficacy profile than the other ARBs in reducing SBP and DBP.
PubMed: 33693183
DOI: 10.1253/circrep.CR-20-0076 -
Journal of Clinical Hypertension... Feb 2011The current study assesses the antihypertensive efficacy and safety of the investigational angiotensin receptor blocker (ARB), azilsartan medoxomil (AZL-M), compared... (Randomized Controlled Trial)
Randomized Controlled Trial
The current study assesses the antihypertensive efficacy and safety of the investigational angiotensin receptor blocker (ARB), azilsartan medoxomil (AZL-M), compared with placebo and the ARB olmesartan medoxomil (OLM-M). This randomized, double-blind, placebo-controlled, multicenter study assessed change from baseline in mean 24-hour ambulatory systolic blood pressure (SBP) following 6 weeks of treatment. Patients with primary hypertension (n=1275) and baseline 24-hour mean ambulatory systolic pressure ≥ 130 mm Hg and ≤ 170 mm Hg were studied; 142 received placebo and the remainder received 20 mg, 40 mg, or 80 mg AZL-M or 40 mg OLM-M. Mean age of participants was 58 ± 11 years, baseline mean 24-hour SBP was 146 mm Hg. Dose-dependent reductions in 24-hour mean SBP at study end occurred in all AZL-M groups. Reduction in 24-hour mean SBP was greater with AZL-M 80 mg than OLM-M 40 mg by 2.1 mm Hg (95% confidence interval, -4.0 to -0.1; P=.038), while AZL-M 40 mg was noninferior to OLM-M 40 mg. The side effect profiles of both ARBs were similar to placebo. AZL-M is well tolerated and more efficacious at its maximal dose than the highest dose of OLM-M.
Topics: Aged; Angiotensin Receptor Antagonists; Argentina; Benzimidazoles; Blood Pressure; Blood Pressure Determination; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Female; Humans; Hypertension; Imidazoles; Male; Mexico; Middle Aged; Oxadiazoles; Peru; Racial Groups; Tetrazoles; Treatment Outcome; United States
PubMed: 21272195
DOI: 10.1111/j.1751-7176.2010.00425.x