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Artificial Cells, Nanomedicine, and... Feb 2018The aim was to enhance the oral bioavailability of olmesartan medoxomil (OM) by preparing solid lipid nanoparticles (SLNs) and comparing with nanosuspension (OM-NS).... (Comparative Study)
Comparative Study
The aim was to enhance the oral bioavailability of olmesartan medoxomil (OM) by preparing solid lipid nanoparticles (SLNs) and comparing with nanosuspension (OM-NS). OM-SLNs and OM-NS were prepared by known methods. Prepared SLNs were evaluated for physical characters and in vivo pharmacokinetic (PK) performance in rats. OM-NS showed more than four-fold increase in the solubility. During DSC and XRD studies, drug incorporated in SLNs was found to be in amorphous form. The relative bioavailability of OM-SLN and OM-NS was 7.21- and 3.52-fold when compared with that of coarse suspension. Further, OM-SLNs also increased the oral bioavailability by two-fold over that of OM-NS.
Topics: Animals; Biological Availability; Drug Carriers; Lipids; Male; Nanoparticles; Olmesartan Medoxomil; Particle Size; Rats; Rats, Wistar; Solubility; Suspensions
PubMed: 28290712
DOI: 10.1080/21691401.2017.1299160 -
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 -
Medicine Apr 2022Diabetic nephropathy (DN) is a common microvascular complication of diabetes, which poses a serious threat to the health and life of patients. There is evidence that...
Effects of α lipoic acid combined with olmesartan medoxomil on blood glucose and oxidation indicators in patients with diabetic nephropathy: A protocol for a parallel, randomized, double-blind, controlled clinical trial.
BACKGROUND
Diabetic nephropathy (DN) is a common microvascular complication of diabetes, which poses a serious threat to the health and life of patients. There is evidence that both α lipoic acid and olmesartan medoxomil have positive effects in the treatment of DN, but whether the 2 have synergistic effects and the effects on blood glucose and oxidation indicators are controversial.
METHODS
This is a prospective parallel, randomized, double-blind, placebo-controlled trial to study the effects of α lipoic acid in combination with olmesartan medoxomil on blood glucose and oxidation indicators in patients with DN. Participants will be randomly assigned to a treatment group, which will receive α lipoic acid dispersive tablets combined with olmesartan medoxomil tablets, or a control group, which will receive olmesartan medoxomil tablets combined with placebo for 4 weeks, followed up for 12 weeks. Observation indicators include: glycemic indicators [fasting blood glucose, 2 hours postprandial blood glucose and glycosylated hemoglobin], the oxidation indicators [serum glutathione, superoxide dismutase, malondialdehyde, 8-hydroxydeox-yguanosine], and adverse reactions. Finally, SPASS 22.0 software will be used for statistical analysis of the data.
DISCUSSION
This study will evaluate the effects of α lipoic acid combined with olmesartan medoxomil on blood glucose and oxidation indicators in patients with DN. The results of this study will provide a reference for the clinical use of α lipoic acid combined with olmesartan medoxomil in the treatment of DN.
TRIAL REGISTRATION
OSF Registration number: DOI 10.17605/OSF.IO/VJWXS.
Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Glucose; Blood Pressure; Diabetes Mellitus; Diabetic Nephropathies; Double-Blind Method; Female; Humans; Hypertension; Imidazoles; Male; Olmesartan Medoxomil; Prospective Studies; Randomized Controlled Trials as Topic; Tetrazoles; Thioctic Acid
PubMed: 35512068
DOI: 10.1097/MD.0000000000029080 -
Drug Development and Industrial Pharmacy Dec 2020The solubility and solution thermodynamic properties of a weakly water-soluble compound olmesartan medoxomil (OLM) in binary 'polyethylene glycol (PEG-400) + water'...
The solubility and solution thermodynamic properties of a weakly water-soluble compound olmesartan medoxomil (OLM) in binary 'polyethylene glycol (PEG-400) + water' cosolvent compositions were determined. The 'mole fraction solubility ( )' of OLM in binary 'PEG-400 + water' cosolvent compositions and pure solvents (PEG-400 and water) was determined at ' = 295.15-330.15 K' and ' = 0.1 MPa'. The Hansen solubility parameter (HSP) of OLM, pure PEG-400, pure water, and binary 'PEG-400 + water' cosolvent compositions free of OLM were also predicted. The obtained values of OLM were correlated using 'van't Hoff, modified Apelblat, Yalkowsky-Roseman, Jouyban-Acree and Jouyban-Acree-van't Hoff' computational models with the error values of <4.0%. The maximum and minimum value of OLM was predicted in neat PEG-400 (1.15 × 10 at = 330.15 K) and neat water (1.90 × 10 at = 295.15 K), respectively. The OLM HSP was predicted to be more close with that of neat PEG-400. The value of OLM was found increased significantly with increase in temperature and PEG-400 mass fraction in all 'PEG-400 + water' cosolvent compositions including neat PEG-400 and neat water. An 'apparent thermodynamic analysis' studies presented an 'endothermic and entropy-driven dissolution' of OLM in all 'PEG-400 + water' cosolvent compositions including pure PEG-400 and pure water.
Topics: Olmesartan Medoxomil; Polyethylene Glycols; Solubility; Solvents; Thermodynamics; Water
PubMed: 33151111
DOI: 10.1080/03639045.2020.1847136 -
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 -
Drug Delivery and Translational Research Mar 2022Hypertension is a common disease for human with high morbidity and mortality, and olmesartan medoxomil (OM) is widely used in the therapy of hypertension. However, poor...
Hypertension is a common disease for human with high morbidity and mortality, and olmesartan medoxomil (OM) is widely used in the therapy of hypertension. However, poor water solubility and low bioavailability limit its widespread use. To improve the effect of OM, a ternary OM solid dispersion consisting of hydroxypropyl-β-cyclodextrin (HP-β-CD) and hydroxypropyl methylcellulose (HPMC) was prepared by mechanochemical method. The best preparation parameters were OM/HP-β-CD/HPMC-E5 with mass ratio of 1:2.6:1 and milling time of 4 h. Under the optimal preparation conditions, the solubility of the ternary solid dispersion could be increased by 12 times as compared with pure OM. Due to the addition of HPMC-E5, the solid dispersion had sustained release performance with prolonged release time of 12 h. Furthermore, in vivo study demonstrated that the prepared solid dispersion could afford significantly improved bioavailability of ~ 3-fold in comparison with pure drug. Hence, the prepared ternary solid dispersion of OM may be a promise delivery system for clinical application.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Oral; Biological Availability; Delayed-Action Preparations; Humans; Hypertension; Hypromellose Derivatives; Olmesartan Medoxomil; Particle Size; Solubility; Technology
PubMed: 33860449
DOI: 10.1007/s13346-021-00959-w -
Luminescence : the Journal of... Dec 2023The present research has established a quick and highly sensitive second-derivative synchronous fluorometric technique for the simultaneous quantification of a binary...
A novel sustainable second-derivative synchronous spectrofluorimetric method for the simultaneous determination of olmesartan medoxomil and rosuvastatin calcium in bulk and formulations: Integrated greenness and whiteness evaluation.
The present research has established a quick and highly sensitive second-derivative synchronous fluorometric technique for the simultaneous quantification of a binary mixture of olmesartan medoxomil and rosuvastatin calcium. Simultaneously, the suggested approach was used to detect the synchronous fluorescence intensity of the cited drugs at Δ λ = 80 nm in ethanol to determine the concentrations of olmesartan medoxomil and rosuvastatin calcium at 265 and 240 nm, respectively. Various experimental conditions were tested, and each variable was analyzed and optimized. The calibration graphs were shown to be linear within ranges of 0.1-2.0 and 0.5-6.0 μg ml for each drug concentration, respectively. The newly developed Green Solvents Selecting Tool (GSST) was utilized to assess the solvent's sustainability. Furthermore, the proposed method was found to be environmentally friendly after being evaluated with three different tools [the Green Analytical Procedure Index (GAPI), the Analytical Greenness Metric (AGREE), and the Analytical Eco-Scale with Eco-score equal to 95]. The whiteness qualities were also studied using the Red-Green-Blue (RGB12) model, which was recently designed and showed a high score equal to 92.9. The proposed method's good findings, as well as its ongoing sustainability, simplicity, and economy, stimulate its application in QC laboratories.
PubMed: 38062646
DOI: 10.1002/bio.4641 -
Spectrochimica Acta. Part A, Molecular... Dec 2023The aim of this study is to develop and validate two simple spectrophotometric methods for simultaneous determination of metoprolol succinate (MET) and olmesartan...
Area under the curve and ratio difference spectrophotometric methods with evaluation of the greenness for simultaneous determination of olmesartan medoxomil and metoprolol succinate.
The aim of this study is to develop and validate two simple spectrophotometric methods for simultaneous determination of metoprolol succinate (MET) and olmesartan medoxomil (OLM) in tablet form. Method (I) was area under the curve (AUC) method. This approach involved the measuring of the area over a variety of wavelengths. Two wavelength ranges; 213-230 nm and 244-266 nm were chosen for determination of MET and OLM, respectively. Method (II) was ratio difference spectrophotometricmethod. For determination of MET, the ratio spectra were generated using 15 μg/mL OLM as a divisor then the peak to trough amplitudes between 221 nm and 245 nm were displayed versus the corresponding concentrations of MET. For determination of OLM, the peak-to-peak amplitudes between 247 and 293 nm were chosen and found to be directly proportional to OLM concentrations using 15 μg/mL MET as a divisor. The linearity ranges were 2-30 μg/mL and 2-25 μg/mL for MET and OLM, respectively. The assay results showed good mean %recovery ± SD as well as good agreement with that of the reported method. The developed methods were validated according to ICH guidelines. The developed methods are accurate, precise, eco-friendly and could be applied successfully to estimate OLM and MET in their combined dosage form.
Topics: Olmesartan Medoxomil; Metoprolol; Spectrophotometry
PubMed: 37499475
DOI: 10.1016/j.saa.2023.123164 -
Basic & Clinical Pharmacology &... Oct 2017Azilsartan (AZL) medoxomil was approved by the United States Food and Drug Administration in 2011 for the treatment of hypertension and has shown promising results both... (Review)
Review
Azilsartan (AZL) medoxomil was approved by the United States Food and Drug Administration in 2011 for the treatment of hypertension and has shown promising results both in blood pressure (BP) reduction and in tolerability, but has not yet been taken into practice to the same extent as other angiotensin II receptor blockers (ARBs) that have been on the market for a longer period. AZL antagonizes the AT receptor for angiotensin II (ANG II), whereas angiotensin-converting enzyme inhibitors block the conversion of angiotensin I to ANG II, but not alternative routes of formation of ANG II. The bioavailability of AZL is about 60% and it has a t of 1.5-3 hr and a half-life of approximately 11 hr. With its IC of 7.4 nM after 5 hr of drug washout in radioligand assays, AZL has a tighter and longer-lasting binding to the AT receptor by several orders of magnitude than other ARBs, which might lead to a more effective reduction in BP. Clinical studies have revealed that AZL doses of 40 and 80 mg/day reduce BP significantly better than maximal clinical doses of valsartan or olmesartan, while being well tolerated and exhibiting a spectrum of adverse effects comparable to those of other ARBs. These properties of AZL might lower the risk of cardiovascular disease and thereby reduce mortality rates. However, the existing mortality studies have not found this correlation, which should be further investigated.
Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Clinical Trials as Topic; Humans; Hypertension; Oxadiazoles; Renin-Angiotensin System; Signal Transduction; Treatment Outcome
PubMed: 28444983
DOI: 10.1111/bcpt.12800 -
The Journal of the Association of... Mar 2024For >3 decades now, angiotensin receptor blockers (ARB) have been used in the management of hypertension (HTN) and HTN-related cardiovascular (CV) diseases. Olmesartan... (Review)
Review
For >3 decades now, angiotensin receptor blockers (ARB) have been used in the management of hypertension (HTN) and HTN-related cardiovascular (CV) diseases. Olmesartan medoxomil (OLM) is an angiotensin II type 1 (AT1) receptor antagonist (or blocker) that binds tightly to the AT1 receptor with long-lasting efficacy over the 24-hour period and safety demonstrated in several trials. It is well tolerated and effective in reducing blood pressure (BP) in mono and combination therapy with thiazide diuretics or calcium channel blockers across a wide range of patient subgroups. The effectiveness and safety of OLM-based combination therapies have good and tolerable profiles with high adherence in the fixed single-pill formulation. Consistent antihypertensive efficacy and good tolerability when used as monotherapy or as a combined therapy make OLM a valuable treatment option for adults with HTN. In this review, we discuss the important clinical implications of OLM as an optimal choice as monotherapy and combination therapy in managing patients with HTN.
Topics: Humans; Hypertension; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Drug Therapy, Combination; Imidazoles; Tetrazoles; Olmesartan Medoxomil
PubMed: 38736121
DOI: 10.59556/japi.72.0480