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Analytical Methods : Advancing Methods... Apr 2024Sartans, as a class of antihypertensive drugs, pose a threat to human health when illegally added to herbal beverages. It is crucial to detect sartans in herbal...
Sartans, as a class of antihypertensive drugs, pose a threat to human health when illegally added to herbal beverages. It is crucial to detect sartans in herbal beverages. We have developed a highly sensitive monoclonal antibody against candesartan (CAN), olmesartan medoxomil (OLM), and irbesartan (IRB), with 50% inhibitory concentrations (IC) that were obtained indirect enzyme-linked immunosorbent assay (ic-ELISA) as 0.178 ng mL, 0.185 ng mL, and 0.262 ng mL against CAN, OLM, and IRB, respectively. Based on this monoclonal antibody, we developed a rapid screening method for CAN, OLM, and IRB in herbal beverage samples using an immunochromatographic assay (ICA) strip. Test for 15 minutes after simple and rapid sample pre-treatment and the results of this method can be obtained through naked eye observation. The detection limits (LODs) of the ICA strip for CAN, OLM, and IRB in herbal beverage samples are lower than 0.15 ng mL, and the results of the ICA strip and ic-ELISA are consistent in spiked samples and recovery experiments. Therefore, this method can quickly, efficiently, and reliably achieve high-throughput on-site rapid detection of illegally added CAN, OLM, and IRB in herbal beverages.
Topics: Humans; Olmesartan Medoxomil; Irbesartan; Angiotensin II Type 1 Receptor Blockers; Beverages; Antibodies, Monoclonal; Benzimidazoles; Biphenyl Compounds; Tetrazoles
PubMed: 38567492
DOI: 10.1039/d4ay00151f -
Frontiers in Pharmacology 2019A new, simple, sensitive, selective, rapid, and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for...
Method Validation for Simultaneous Quantification of Olmesartan and Hydrochlorothiazide in Human Plasma Using LC-MS/MS and Its Application Through Bioequivalence Study in Healthy Volunteers.
A new, simple, sensitive, selective, rapid, and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for simultaneous quantification of Olmesartan and hydrochlorothiazide in human plasma. Simple liquid-liquid extraction procedure was applied for plasma sample pretreatment using a mixture of diethyl ether and dichloromethane, as an extraction solution. Analytes were separated on UNISOL C18 150*4.6 mm, 5 µm column using methanol, and 2 mM ammonium acetate pH 5.5 (80:20, v/v) as a mobile phase and detected by electrospray ionization in the multiple reaction monitoring (MRM) mode. The mass transition ion pairs were followed in negative ion mode as m/z 445.20 → 148.90 for Olmesartan; m/z 451.40 → 154.30 for Olmesartan D and m/z 295.80 → 205.10 for hydrochlorothiazide; m/z 298.90 → 206.30 for hydrochlorothiazide C D. The method showed excellent linearity ( > 0.99) over the concentration range of 5.002-2,599.934 ng/ml for Olmesartan and from 3.005 to 499.994 ng/ml for hydrochlorothiazide. Precision (% CV) and accuracy (% bias) for Olmesartan were found in the range of 3.07-9.02% and -5.00-0.00%, respectively. Precision (% CV) and accuracy (% bias) for hydrochlorothiazide were found in the range of 3.32-8.21% and 1.99-3.80%, respectively. This as developed novel and high-throughput liquid-liquid extraction bioanalytical method has substantial innovative value with the benefits of cost effectiveness, good extraction efficiency, shorter analysis run time, low organic solvent consumption, and simpler procedure over the previously reported solid-phase extraction method. The application of this method in pharmacokinetic studies was further demonstrated successfully through a bioequivalence study conducted on healthy human subjects, following oral administration of combined formulation of Olmesartan medoxomil and hydrochlorothiazide in fixed-dose tablet.
PubMed: 31396085
DOI: 10.3389/fphar.2019.00810 -
Drug Development and Industrial Pharmacy Aug 2019Olmesartan medoxomil (OM) is a hydrophobic antihypertensive drug with low bioavailability (26%) and is known to have adverse effects such as celiac disease and...
Olmesartan medoxomil (OM) is a hydrophobic antihypertensive drug with low bioavailability (26%) and is known to have adverse effects such as celiac disease and enteropathy. The purpose of this study was to develop SMEDDS to increase bioavailability and decrease potential side effects of OM. Hydrophilic lipophilic balance was calculated by testing solubility of OM in different oils, surfactants, and cosurfactants to obtain the most suitable combination of SMEDDS. Pseudoternary phase diagram was used to select the better oil/water formulation of SMEDDS. After a test for 3-month stability, dissolution tests and parallel artificial membrane permeability assay (PAMPA) were conducted to investigate drug solubility and permeability. Biodistribution of fluorescent marked SMEDDS was observed by using imaging system. The pharmacodynamics of the drug were determined by measuring blood pressure from tails of rats. At the end of the experiment, intestines were examined for adverse effects of OM. Compared with tablet formulation according to the dissolution study, SMEDDS formulation showed 1.67 times improvement in solubility of OM. PAMPA studies suggested a much faster permeability rate for OM SMEDDS compared to the suspension form. Labeled SMEDDS gave 3.96 times stronger fluorescent emission than control dye administered mice in imaging system (IVIS) studies, indicating an increased bioavailability. Treating effect of SMEDDS was 3.1 times more efficient compared to suspension in hypertensive rats. It caused neither celiac-like enteropathy nor diarrhea, during 21-day noninvasive blood pressure system (NIBP) assay. Our results suggest that SMEEDS formulation improves dissolution and oral bioavailability of OM while reducing its adverse effects.
Topics: Administration, Oral; Animals; Biological Availability; Chemistry, Pharmaceutical; Drug Delivery Systems; Emulsions; Hydrophobic and Hydrophilic Interactions; Male; Mice; Oils; Olmesartan Medoxomil; Particle Size; Rats; Rats, Wistar; Solubility; Surface-Active Agents; Suspensions; Tablets; Tissue Distribution
PubMed: 30986085
DOI: 10.1080/03639045.2019.1607868 -
High Blood Pressure & Cardiovascular... May 2021Essential hypertension is the most common cardiovascular (CV) risk factor, being primarily involved in the pathogenesis of CV disease and mortality worldwide. Given the... (Review)
Review
Essential hypertension is the most common cardiovascular (CV) risk factor, being primarily involved in the pathogenesis of CV disease and mortality worldwide. Given the high prevalence and growing incidence of this clinical condition in the general population in both high and low-income countries, antihypertensive drug therapies are frequently prescribed in different hypertension-related CV diseases and comorbidities. Among these conditions, evidence are available demonstrating the clinical benefits of lowering blood pressure (BP) levels, particularly in those hypertensive patients at high or very high CV risk profile. Preliminary studies, performed during the Sars-COVID-19 epidemic, raised some concerns on the potential implication of hypertension and antihypertensive medications in the susceptibility of having severe pneumonia, particularly with regard to the use of drugs inhibiting the renin-angiotensin system (RAS), including angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). These hypotheses were not confirmed by subsequent studies, which independently and systematically demonstrated no clinical harm of these drugs also in patients with Sars-COVID-19 infection. The aim of this narrative review is to critically discuss the available evidence supporting the use of antihypertensive therapies based RAS blocking agents in hypertensive patients with different CV risk profile and with additional clinical conditions or comorbidities, including Sars-COVID-19 infection, with a particular focus on single-pill combination therapies based on olmesartan medoxomil.
Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; COVID-19; Comorbidity; Humans; Hypertension; Olmesartan Medoxomil; Pandemics; Pneumonia, Viral; Renin-Angiotensin System; SARS-CoV-2
PubMed: 33710599
DOI: 10.1007/s40292-021-00443-z -
Molecules (Basel, Switzerland) May 2024Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor...
Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated β-cyclodextrin (RM-β-CD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG-thermogravimetry; DTG-derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an -type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host-guest system OLM/RM-β-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-β-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.
Topics: beta-Cyclodextrins; Olmesartan Medoxomil; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction; Thermogravimetry; Models, Molecular
PubMed: 38792072
DOI: 10.3390/molecules29102209 -
Kyobu Geka. the Japanese Journal of... Sep 2020We evaluated the blood pressure( BP) lowering effect and possible suppression of aortic enlargement by olmesartan (OLM) in patients with thoracic and thoracoabdominal...
[Effects of Olmesartan Medoxomil on Patients with Thoracic and Thoracoabdominal Aortic Aneurysm;Evaluation of Anti-hypertensive Effect and Possible Suppression of Aneurysmal Dilation( OLM 40 Study)].
We evaluated the blood pressure( BP) lowering effect and possible suppression of aortic enlargement by olmesartan (OLM) in patients with thoracic and thoracoabdominal aortic aneurysm. In this single center prospective, forced titration study, 50 patients were registered between 2008 and 2011. After all patients received any of OLM 10, 20, and 40 mg/day as an initial dose, the dosage of OLM was titrated up to 40 mg as needed during follow-up period. Home BP (HBPs), aortic aneurysm size assessed by computed tomography (CT) scan, indices of renal function were recorded at 3- and 6-months follow-up. Depending on whether 40 mg/day of prescription was continued for more than 4 months or not, the patients were divided into 2 groups:less than 40 mg (<40 mg) and 40 mg groups. Morning HBPs tended to decrease in both groups, and the percent changes in BPs were essentially the same regardless of dosage. The absolute value of aortic diameter tended to slightly enlarge only in <40 mg group. Also in the <40 mg group, the absolute differences in aortic diameter between those at the time of study registration and each follow-up were 0.5±1.8 mm at 3-month and 1.2±2.3 mm at 6-month (p=0.047),whereas the percent changes were 0.9±3.3% and 2.2±4.5% at 3 and 6 months, respectively( p=0.058). As for 40 mg group, the absolute differences and percent changes did not reach statistically significant increase during the follow-up period. No severe renal dysfunction related to OLM 40 mg prescription was observed. Our results imply that OLM 40 mg may suppress aortic aneurysmal dilation independently of blood pressure lowering effect. Further study with larger number of sample size is warranted to assure this observation.
Topics: Antihypertensive Agents; Aortic Aneurysm, Thoracic; Dilatation; Humans; Hypertension; Imidazoles; Olmesartan Medoxomil; Prospective Studies; Tetrazoles
PubMed: 32879267
DOI: No ID Found -
International Journal of Molecular... Oct 2022A worldwide crisis with nitrosamine contamination in medical products began in 2018. Therefore, trace-level analysis of nitrosamines is becoming an emerging topic of...
A worldwide crisis with nitrosamine contamination in medical products began in 2018. Therefore, trace-level analysis of nitrosamines is becoming an emerging topic of interest in the field of quality control. A novel GC-MS method with electron ionization and microextraction was developed and validated for simultaneous determination of nine carcinogenic nitrosamines (NDMA, NMEA, NDEA, NDBA, NMOR, NPYR, NPIP, NDPA, and -methyl-npz) in active pharmaceutical ingredients (APIs): cilostazol, sunitinib malate, and olmesartan medoxomil. The method was validated according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, demonstrating good linearity in the range of LOQ up to 21.6 ng/mL (120% of specification limit). The limits of detection for the nine nitrosamines were determined to be in the range 0.15-1.00 ng/mL. The developed trace level GC-MS method turned out to be specific, accurate, and precise. The accuracy of all the tested APIs ranged from 94.09% to 111.22% and the precision evaluated by repeatability, intermediate precision, and system precision was RSD ≤ 7.65%. Nitrosamines were not detected in cilostazol and sunitinib, whereas in olmesartan medoxomil NDEA was detected at the level of LOQ. The novel protocol was successfully applied for nitrosamines determination in selected APIs and can be used for the routine quality control of APIs under Good Manufacturing Practices rules, ensuring the safety and effectiveness of pharmaceutical products.
Topics: Humans; Nitrosamines; Gas Chromatography-Mass Spectrometry; Sunitinib; Cilostazol; Tandem Mass Spectrometry; DNA Damage; Olmesartan Medoxomil; Pharmaceutical Preparations
PubMed: 36292981
DOI: 10.3390/ijms232012125 -
Kardiologiia Dec 2023Aim A 12-month evaluation of the potentialities of the angiotensin II receptor inhibitor olmesartan (Olme) and the angiotensin receptor and neprilysin...
The Clinical Evolution of Diffuse Myocardial Fibrosis in Patients With Arterial Hypertension and Heart Failure With Mildly Reduced Ejection Fraction Treated by Olmesartan or Sacubitril / Valsartan.
Aim A 12-month evaluation of the potentialities of the angiotensin II receptor inhibitor olmesartan (Olme) and the angiotensin receptor and neprilysin inhibitor (ARNI) sacubitril/valsartan in patients with arterial hypertension (AH) and dyslipidemia in the dynamics of the following indicators of chronic heart failure (CHF): N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), LV global longitudinal strain (LV GLS) in diffuse myocardial fibrosis (MF) previously diagnosed by magnetic resonance imaging (MRI).Material and methods Olmesartan medoxomil (n=56) and sacubitril/valsartan (n=63) were used for 12 months in patients with hypertension, dyslipidemia and NYHA functional class II-III CHF with mid-range LVEF (CHFmrEF). MF was diagnosed by the following MRI criteria: late gadolinium enhancement and an increased proportion of extracellular matrix (33% or more). The frequency of persisting late gadolinium enhancement and the increased proportion of extracellular matrix (33% or more) was evaluated at 12 months; changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), NT-proBNP, and LV GLS were evaluated after 3, 6, and 12 months of follow-up.Results Baseline parameters did not differ between groups. The late gadolinium enhancement and increased proportion of extracellular matrix were present at baseline in all patients of both groups (100%; p=1.0). Already at 3 months, statistically significant decreases in SBP and DBP were observed in both groups. In addition, the LV GLS monitoring showed LV GLS significantly increased in both groups after 3 months and continued changing after 6 and 12 months. The NT-proBNP concentration significantly decreased in both groups already after 3 months and continued to decrease after 6 and 12 months. At 6 and 12 months, sacubitril/valsartan was superior to olmesartan in reducing SBP and NT-proBNP and in restoring LV GLS. At 12 months, the incidence of persisting, abnormal late gadolinium enhancement and increased proportion of extracellular matrix was significantly less in the ARNI group.Conclusion Olmesartan was demonstrated effective in the multi-modality therapy of CHFmrEF and MF in patients with AH and dyslipidemia. ARNI was superior to olmesartan in this regard, but further research of this issue is required.
Topics: Humans; Stroke Volume; Contrast Media; Gadolinium; Angiotensin Receptor Antagonists; Ventricular Function, Left; Valsartan; Tetrazoles; Heart Failure; Aminobutyrates; Biphenyl Compounds; Hypertension; Ventricular Dysfunction, Left; Drug Combinations; Fibrosis; Dyslipidemias
PubMed: 38156487
DOI: 10.18087/cardio.2023.12.n2557 -
The Journal of the Association of... Aug 2020Real-world data on the effectiveness of antihypertensive drugs (AHDs) in India is limited. The present study aims to provide updated evidence regarding the effectiveness... (Observational Study)
Observational Study
BACKGROUND
Real-world data on the effectiveness of antihypertensive drugs (AHDs) in India is limited. The present study aims to provide updated evidence regarding the effectiveness of olmesartan as monotherapy or in combination with other AHDs in Indian patients with essential hypertension.
METHODS
Electronic medical record data of adult patients who were diagnosed with essential hypertension (≥140/90 mmHg) and were prescribed olmesartan as mono- or add-on therapy were retrospectively analyzed. Patients were classified based on the number of AHD classes prescribed on initiation of olmesartan. Change in systolic and diastolic blood pressure (SBP and DBP) from baseline was the primary endpoint. Secondary endpoint was evaluation of proportion of patients who achieved treatment goals as per 2018 European Society of Cardiology/European Society of Hypertension guidelines. Readings were obtained before initiating olmesartan and after at least a month of therapy with olmesartan.
RESULTS
Among the 459 included patients, majority were on olmesartan monotherapy or olmesartan+1AHD (91.7%). Mean (95% confidence interval [CI]) change in olmesartan monotherapy group was: SBP (-13.4 [-15.7, -11.1] mmHg) and DBP (-8.3 [-9.5, -7.1] mmHg) and mean (95% CI) change in olmesartan+1AHD group was: SBP (-11.7 [-15.1, -8.3] mmHg) and DBP (-6.6 [-8.3, -4.9] mmHg) (P<0.001 for all). SBP and DBP goals were achieved by 40.4% and 50.3% of patients on olmesartan monotherapy and by 36.1% and 46.2% of patients on olmesartan+1AHD. Among patients with comorbid diabetes, mean (95% CI) change in olmesartan monotherapy group was: SBP (-15.5 [-18.6, -12.4] mmHg) and DBP (-8.7 [-10.2, -7.2] mmHg) and mean (95% CI) change in olmesartan+1AHD group was: SBP (-13.5 [-18.3, -8.7] mmHg) and DBP (-7.6 [-9.8, -5.4] mmHg) (P<0.001 for all). SBP and DBP goals were achieved by 38.5% and 49.4% of patients on olmesartan monotherapy and by 31.7% and 42.9% of patients on olmesartan+1AHD.
CONCLUSION
Olmesartan prescribed as mono- or add-on therapy during routine clinical practice significantly reduced blood pressure in Indian patients with essential hypertension as well as in patients with comorbid diabetes.
Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Electronic Health Records; Humans; Hypertension; Imidazoles; India; Olmesartan Medoxomil; Retrospective Studies; Tetrazoles
PubMed: 32738844
DOI: No ID Found -
European Journal of Preventive... Aug 2023Intensive systolic blood pressure (SBP) lowering has been increasingly used; however, data is missing on patients who had target-achieved (TA). This study aims to show...
Achieved systolic blood pressure and cardiovascular outcomes in 60-80-year-old patients: the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial.
AIMS
Intensive systolic blood pressure (SBP) lowering has been increasingly used; however, data is missing on patients who had target-achieved (TA). This study aims to show the cardiovascular effect of maintaining SBP at intensive levels.
METHODS
The Strategy of Blood Pressure Intervention in Elderly Hypertensive Patients (STEP) trial was a multicentre, randomized, controlled trial which enrolled 8511 young-older (60-80 years) hypertensive patients without prior stroke to compare the cardiovascular prognosis of the intensive treatment (SBP target, 110 to <130 mmHg) vs. the standard treatment (130 to <150 mmHg). This secondary analysis assessed data in patients who achieved a mean SBP within target values. The association of mean achieved SBP and cardiovascular events was examined using a cubic spline function.
RESULTS
In total, 3053 patients (72.0%) in the intensive-treatment group and 3427 (80.3%) in the standard-treatment group had an SBP target achieved, with mean follow-up SBP values of 124.2 mmHg and 137.4 mmHg, respectively. Throughout the median 3.38-year follow-up, the cardiovascular risk was significantly lower in the TA intensive-treatment group than in the TA standard-treatment group [adjusted hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.46-0.80; P < 0.001]. In the intensive-treatment group, patients failing to achieve SBP targets presented higher cardiovascular risk than those TA patients (HR 2.04, 95% CI 1.44-2.88; P < 0.001). A J-shaped relationship was observed between the mean achieved SBP and risk of cardiovascular events, with the lowest risk at an SBP of 126.9 mmHg.
CONCLUSIONS
Maintaining SBP at <130 mmHg offers additional cardiovascular benefits among young-older patients with hypertension.
REGISTRATION
ClinicalTrials.gov: NCT03015311.
PubMed: 37172116
DOI: 10.1093/eurjpc/zwad142