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Therapeutic Advances in Cardiovascular... Aug 2012This is a prespecified subgroup analysis in Hispanic and non-Hispanic patients of a study that evaluated blood pressure (BP) control with fixed-dose...
Efficacy and tolerability of fixed-dose amlodipine/olmesartan medoxomil with or without hydrochlorothiazide in Hispanic and non-Hispanic patients whose blood pressure is uncontrolled on antihypertensive monotherapy.
OBJECTIVES
This is a prespecified subgroup analysis in Hispanic and non-Hispanic patients of a study that evaluated blood pressure (BP) control with fixed-dose amlodipine/olmesartan medoxomil (AML/OM)-based therapy in patients whose condition was uncontrolled on prior monotherapy.
METHODS
In this prospective, open-label, dose-titration study, patients with uncontrolled BP after at least 1 month of antihypertensive monotherapy were switched to fixed-dose AML/OM 5/20 mg. Patients were uptitrated to AML/OM 5/40 and 10/40 mg, with uptitration to AML/OM + hydrochlorothiazide 10/40 + 12.5 mg and 10/40 + 25 mg to achieve target BP. The primary efficacy endpoint was the cumulative proportion of patients achieving seated cuff systolic BP (SeSBP) less than 140 mmHg (<130 mmHg in patients with diabetes mellitus) at 12 weeks. Secondary endpoints included SeBP goal rates, ambulatory BP (ABP) target rates, and mean change from baseline in seated cuff BP (SeBP) and ABP at weeks 12 and 20.
RESULTS
Mean baseline BP was similar in Hispanics (153.6/92.8 mmHg; n = 105) and non-Hispanics (153.7/91.8 mmHg; n = 894). At 12 weeks, 72.0% of Hispanics and 76.3% of non-Hispanics achieved the primary endpoint. At week 12, goal rates for cumulative SeBP (<140/90 mmHg or <130/80 mmHg in patients with diabetes) were 69.0% and 71.5% in Hispanic and non-Hispanic patients, respectively. Mean change in SeBP in Hispanics ranged from -15.3/-7.3 mmHg for AML/OM 5/20 mg to -23.2/-13.8 mmHg for AML/OM 10/40 mg + hydrochlorothiazide 25 mg, and in non-Hispanics from -14.1/-7.8 mmHg to -25.4/-13.7 mmHg (all p < 0.0001 versus baseline). A majority of patients achieved mean 24 h, daytime, and nighttime ABP targets in both subgroups. Greater proportions of Hispanics achieved ABP targets versus non-Hispanics at week 12; however, this trend was reversed at week 20. Treatment was well tolerated.
CONCLUSIONS
Switching to a fixed-dose combination of AML/OM ± hydrochlorothiazide provided significant BP lowering and effectively controlled BP in a large proportion of Hispanic and non-Hispanic patients with hypertension uncontrolled on previous monotherapy.
Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Therapy, Combination; Female; Hispanic or Latino; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Middle Aged; Olmesartan Medoxomil; Prospective Studies; Tetrazoles
PubMed: 22855062
DOI: 10.1177/1753944712452190 -
Pharmaceutical Methods Jul 2012A simple, rapid, precise and isocratic RP-HPLC (Reverse Phase High Performance Liquid Chromatography) method is aimed to develop for the simultaneous estimation of...
Development and validation of a stability indicating RP-HPLC method for simultaneous estimation of Olmesartan Medoxomil and Metoprolol Succinate in pharmaceutical dosage form.
AIM AND BACKGROUND
A simple, rapid, precise and isocratic RP-HPLC (Reverse Phase High Performance Liquid Chromatography) method is aimed to develop for the simultaneous estimation of Olmesartan Medoxomil and Metoprolol Succinate in bulk drug and pharmaceutical dosage form.
MATERIALS AND METHODS
The quantification is carried out using YMC-Pack CN (250 × 4.6 mm, 5.0 μm) column and the mobile phase comprises of 0.05% Trifluoro acetic acid (TFA) and Acetonitrile (ACN) (70:30 v/v). The flow rate is 1.0 ml/min. The eluent is monitored at 220 nm. The retention times of Olmesartan Medoxomil and Metoprolol Succinate are 7.9 min and 4.1 min respectively. The method is validated in terms of linearity, precision, accuracy, specificity, limit of detection and limit of quantitation.
RESULTS
Linearity and percentage recoveries of both Olmesartan Medoxomil and Metoprolol Succinate are in the range of 5-35 μg/ml and 100 ± 2%, respectively. The stress testing of both the drugs individually and their mixture is carried out under acidic, alkaline, oxidation, photo-stability and thermal degradation (dry heat and wet heat) conditions and its degradation products are well resolved from the analyte peaks.
CONCLUSION
This method was successfully validated for accuracy, precision, and linearity.
PubMed: 23781484
DOI: 10.4103/2229-4708.103880 -
Journal of the... Dec 2015The pathophysiological role of oxidative stress (OxSt) in hypertension and target organ damage is recognized. Angiotensin II (Ang II) induces OxSt via NAD(P)H oxidase...
The blocking of angiotensin II type 1 receptor and RhoA/Rho kinase activity in hypertensive patients: Effect of olmesartan medoxomil and implication with cardiovascular-renal remodeling.
HYPOTHESIS/INTRODUCTION
The pathophysiological role of oxidative stress (OxSt) in hypertension and target organ damage is recognized. Angiotensin II (Ang II) induces OxSt via NAD(P)H oxidase activation and production of proinflammatory cytokines/growth factors leading to cardiovascular-renal remodeling. Ang II stimulates the RhoA/Rho kinase (ROCK) pathway, which is deeply involved in the development of cardiovascular-renal remodeling via OxSt induction. Olmesartan, an Ang II type 1 receptor blocker, possesses antioxidant and activating nitric oxide system-related effects, which we have shown in terms of p22(phox) reduction, heme oxygenase-1 and calcitonin gene-related peptide increase. This study evaluates in 15 untreated hypertensive patients the effect of olmesartan treatment on p63RhoGEF, key in Ang II-induced ROCK activation, and MYPT-1 phosphorylation, a marker of ROCK activity.
MATERIALS AND METHODS
The p63RhoGEF protein level and MYPT-1 phosphorylation (Western blot) were evaluated at baseline, and after three and six months of olmesartan treatment.
RESULTS
Olmesartan normalized systolic and diastolic BP (p < 0.001), reduced p63RhoGEF level: 1.3±0.25 d.u. (baseline) vs 1.0±0.29 (three months), p < 0.0001 vs 1.0±0.22, (six months), p < 0.0001 and MYPT-1 phosphorylation: 1.2 ±0.14 (baseline) vs 0.9±0.19 (three months), p = 0.008, vs 0.8±0.16 (six months), p = 0.001.
CONCLUSIONS
These data added to our previous results further provide a mechanistic rationale for olmesartan's antioxidant/anti-inflammatory potential translation, in the long term, toward anti-atherosclerotic/anti-remodeling effects reported by clinical trials.
Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Cardiovascular System; Densitometry; Diastole; Female; Humans; Hypertension; Kidney; Male; Middle Aged; Myosin-Light-Chain Phosphatase; Olmesartan Medoxomil; Phosphorylation; Receptor, Angiotensin, Type 1; Rho Guanine Nucleotide Exchange Factors; Systole; rho-Associated Kinases; rhoA GTP-Binding Protein
PubMed: 26240115
DOI: 10.1177/1470320315594324 -
Pharmaceutical Methods Jan 2012A simple, rapid, accurate, precise, and economical UV spectrophotometric method for the simultaneous determination of metoprolol succinate (METO) and olmesartan...
INTRODUCTION
A simple, rapid, accurate, precise, and economical UV spectrophotometric method for the simultaneous determination of metoprolol succinate (METO) and olmesartan medoxomil (OLME) in a combined tablet dosage form using the simultaneous equation method has been developed.
MATERIALS AND METHODS
The method is based on the simultaneous equations for analysis of both the drugs using distilled water as a solvent. METO has absorbance maxima at 221 nm and OLME has absorbance maxima at 257 nm in distilled water.
RESULTS
The linearity was obtained in the concentration range of 5-25 μg/ml and 4-20 μg/ml for METO and OLME, respectively. The concentrations of the drugs were determined by using the simultaneous equations method. The mean recovery was 100.90 ± 1.76 and 100.26 ± 0.71 for METO and OLME, respectively.
CONCLUSION
The method was found to be simple, accurate, and precise and was applicable for the simultaneous determination of METO and OLME in the pharmaceutical tablet dosage form. The results of analysis have been validated statistically and by recovery studies.
PubMed: 23781477
DOI: 10.4103/2229-4708.97724 -
Journal of Hypertension Apr 2016Angiotensin receptor blockers (ARBs) are preferred antihypertensive therapies in patients with type 2 diabetes mellitus (T2DM). Azilsartan medoxomil (AZL-M) is a potent... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Angiotensin receptor blockers (ARBs) are preferred antihypertensive therapies in patients with type 2 diabetes mellitus (T2DM). Azilsartan medoxomil (AZL-M) is a potent ARB for the treatment of stages 1-2 hypertension. We compared the efficacy, safety, and metabolic effects of AZL-M to both valsartan (VAL) and olmesartan (OLM), separately in patients with impaired fasting glucose (prediabetes mellitus) and T2DM.
METHODS
A pooled analysis of 3821 patients from three separate randomized placebo-controlled trials comparing the effects of AZL-M (40 and 80 mg), OLM (40 mg), VAL (320 mg), and placebo on changes in ambulatory and clinic blood pressure (BP) among patients with hypertension and prediabetes mellitus or T2DM was performed. Two analysis pools were created to facilitate comparisons: Pool A included patients who received placebo, AZL-M or OLM and Pool B included those who received AZL-M or VAL. Within each pool, patients were stratified by glycemic subgroups (normoglycemic, prediabetes mellitus, or T2DM) based on hemoglobin A1c values. Changes from baseline in both 24-h and clinic SBP were the primary efficacy assessments.
RESULTS
Baseline 24-h mean SBPs were approximately 145 and 146 mmHg in the prediabetes mellitus and T2DM subgroups, respectively; corresponding clinic SBPs were approximately 158 and 159 mmHg. Baseline hemoglobin A1c values for each subgroup (both pools) were normoglycemic, 5.3%; prediabetes mellitus, 6.0%; and T2DM, 6.9%. Changes from baseline in 24-h or clinic SBP were significantly greater with AZL-M, 80 mg compared with either OLM 40 mg or VAL 320 mg in all subgroups in each pool. Safety and tolerability were similar among the active treatment and placebo subgroups.
CONCLUSION
These analyses indicate that AZL-M, 80 mg/day lowers SBP by a greater magnitude than OLM or VAL at maximally approved doses in patients with prediabetes mellitus and T2DM. These findings have important clinical implications for this high-risk patient group.
Topics: Adult; Aged; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Diabetes Mellitus, Type 2; Female; Humans; Imidazoles; Male; Middle Aged; Oxadiazoles; Prediabetic State; Tetrazoles; Valsartan
PubMed: 26766564
DOI: 10.1097/HJH.0000000000000839 -
Indian Journal of Pharmacology 2013Olmesartan medoxomil is an angiotensin receptor blocker (ARB) which is shown to be effective and well tolerated in hypertensive patients. It is a frequently prescribed...
Olmesartan medoxomil is an angiotensin receptor blocker (ARB) which is shown to be effective and well tolerated in hypertensive patients. It is a frequently prescribed antihypertensive as it is considered safe. Here, we report the case of a patient who developed maculopapular rash during the course of the treatment with olmesartan medoxomil.
Topics: Angiotensin II Type 1 Receptor Blockers; Drug Eruptions; Female; Humans; Hypertension; Imidazoles; Middle Aged; Tetrazoles
PubMed: 23716904
DOI: 10.4103/0253-7613.108325 -
International Journal of Nanomedicine 2019Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability due to extensive first-pass metabolism. This study aimed to prepare transetho somes...
INTRODUCTION AND AIM
Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability due to extensive first-pass metabolism. This study aimed to prepare transetho somes (TEs) for enhancing the transdermal delivery of OLM to avoid its oral problems.
METHODS
TE formulae were prepared utilizing 51.31 full factorial design using various surfactants (SAAs) and different phospholipid-to-SAA ratios. The formulae were characterized regarding their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and the amount of drug released after 6 hours (Q6h). Design Expert software was employed to select the optimum formula.
RESULTS
The optimum formula (TE14) had an EE% of 58.50%±1.30%, PS of 222.60±2.50 nm, PDI of 0.11±0.06, ZP of -20.80±0.30 mV, and Q6h of 67.40%±0.20%. In addition, TE14 was compared to transferosomes (TFs) in terms of elasticity and was found to show higher deformability index. Further, evaluation of ex vivo permeation using both rat and shed snake skin showed higher permeability of TE14 compared to TFs and OLM suspension. Confocal laser scanning microscopy confirmed the capability of the fluorolabeled TE14 to penetrate deep within the skin, while the histopathological study confirmed its safety. TE14 successfully maintained normal blood pressure values of rats up to 24 hours. Moreover, TE14 showed superiority in dermatokinetic study when compared with drug suspension.
CONCLUSION
Taken together, the obtained results confirmed the potential of employing TEs as a successful carrier for the transdermal delivery of OLM.
Topics: Administration, Cutaneous; Animals; Antihypertensive Agents; Blood Pressure; Calorimetry, Differential Scanning; Drug Delivery Systems; Drug Stability; Elasticity; Factor Analysis, Statistical; Liposomes; Male; Methylprednisolone; Olmesartan Medoxomil; Rats, Wistar; Skin; Snakes
PubMed: 30936696
DOI: 10.2147/IJN.S196771 -
Pharmaceutics Jun 2016The main purpose of this study was to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of Olmesartan (OLM) for enhancement of its solubility and...
Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation.
The main purpose of this study was to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of Olmesartan (OLM) for enhancement of its solubility and dissolution rate. In this study, liquid SNEDDS containing Olmesartan was formulated and further developed into a solid form by the spray drying technique using Aerosil 200 as a solid carrier. Based on the preliminary screening of different unloaded SNEDDS formulae, eight formulae of OLM loaded SNEEDS were prepared using Capryol 90, Cremophor RH40 and Transcutol HP as oil, surfactant and cosurfactant, respectively. Results showed that the mean droplet size of all reconstituted SNEDDS was found to be in the nanometric range (14.91-22.97 nm) with optimum PDI values (0.036-0.241). All formulae also showed rapid emulsification time (15.46 ± 1.34-24.17 ± 1.47 s), good optical clarity (98.33% ± 0.16%-99.87% ± 0.31%) and high drug loading efficiency (96.41% ± 1.20%-99.65% ± 1.11%). TEM analysis revealed the formation of spherical and homogeneous droplets with a size smaller than 50 nm. In vitro release of OLM from SNEDDS formulae showed that more than 90% of OLM released in approximately 90 min. Optimized SNEDDS formulae were selected to be developed into S-SNEDDS using the spray drying technique. The prepared S-SNEDDS formulae were evaluated for flow properties, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), reconstitution properties, drug content and in vitro dissolution study. It was found that S-SNEDDS formulae showed good flow properties and high drug content. Reconstitution properties of S-SNEDDS showed spontaneous self-nanoemulsification and no sign of phase separation. DSC thermograms revealed that OLM was in solubilized form and FTIR supported these findings. SEM photographs showed smooth uniform surface of S-SNEDDS with less aggregation. Results of the in vitro drug release showed that there was great enhancement in the dissolution rate of OLM. To clarify the possible improvement in pharmacokinetic behavior of OLM S-SNEDDS, plasma concentration-time curve profiles of OLM after the oral administration of optimized S-SNEDDS formula (F3) were compared to marketed product and pure drug in suspension. At all time points, it was observed that OLM plasma concentrations in rats treated with S-SNEDDS were significantly higher than those treated with the drug in suspension and marketed product.
PubMed: 27355963
DOI: 10.3390/pharmaceutics8030020 -
Cardiorenal Medicine Dec 2012Cardiorenal metabolic syndrome (CRS) is a global health care concern in view of aging in certain populations, increased obesity, changing lifestyles, and its close...
Improved Identification and Antihypertension Pharmacotherapy in Cardiorenal Metabolic Syndrome: Focus on Racial/Ethnic Minorities, Olmesartan Medoxomil, and Combination Therapy.
Cardiorenal metabolic syndrome (CRS) is a global health care concern in view of aging in certain populations, increased obesity, changing lifestyles, and its close association with type 2 diabetes mellitus and cardiovascular morbidity and mortality. Determining the appropriate criteria for CRS has been somewhat controversial, and efforts to fully describe and define the syndrome are still ongoing. Nonetheless, improving knowledge of the syndrome among health care professionals will help to identify patients who may require pharmacological and therapeutic lifestyle intervention, particularly with regards to addressing high-normal blood pressure and hypertension. This article reviews current clinical guidelines with a focus on the identification, especially in racial/ethnic minorities, treatment, and associated cardiovascular morbidity and mortality of high blood pressure and hypertension in patients with CRS. Efficacy and outcomes studies that provide insight into the selection of an initial antihypertensive regimen in this population will be discussed. Finally, a brief review of the benefits of olmesartan medoxomil and combination therapy and patient factors in the management of hypertension with CRS will be addressed.
PubMed: 23380878
DOI: 10.1159/000342968 -
Scientia Pharmaceutica 2015Drug product purity and potency are of most significance in the regulatory market as we notice many recalled batches worldwide, particularly in the US and Japan....
Drug product purity and potency are of most significance in the regulatory market as we notice many recalled batches worldwide, particularly in the US and Japan. Olmesartan Medoxomil is an anti-hypertensive drug. The present invention relates to a process for the preparation of Olmesartan Medoxomil with 99.9% purity in an overall 62% yield. The synthesis includes three isolations and one purification with easy plant operations. This process describes the formation and control of each individual impurity in all stages. This process for Olmesartan Medoxomil and its intermediates is competent for industrial production in very short reaction time intervals with an appreciable yield and high purity.
PubMed: 26839831
DOI: 10.3797/scipharm.1502-04