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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 -
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 -
BMJ Case Reports Apr 2024This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman...
This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman who consumed an overdose of multiple medications: nifedipine, azelnidipine, amlodipine besylate, olmesartan medoxomil, telmisartan, esaxerenone and vildagliptin. She presented with haemodynamic instability, necessitating intubation. Despite stabilising haemodynamic parameters within 24 hours, she manifested escalating extremity oedema. At 52 hours after ingestion, mottled skin was observed, along with necrotic alterations in the swollen hands and compartment pressures exceeding 30 mm Hg in all extremities. ACS was diagnosed, leading to fasciotomies. The aetiology is postulated to be drug-induced angio-oedema, possibly intensified by the concurrent overdose of olmesartan medoxomil, telmisartan and vildagliptin, each of which has a risk of angio-oedema even at standard dosages. This scenario is a very rare case caused by drug-induced angio-oedema, which underscores the importance of vigilant monitoring to detect ACS in patients with progressing limb oedema.
Topics: Middle Aged; Female; Humans; Olmesartan Medoxomil; Telmisartan; Vildagliptin; Polypharmacy; Amlodipine; Drug Overdose; Angioedema; Tetrazoles; Antihypertensive Agents; Hypertension
PubMed: 38569737
DOI: 10.1136/bcr-2023-259485 -
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 -
Pharmaceutical Research May 2024Olmesartan medoxomil (olmesartan-MX), an ester-type prodrug of the angiotensin II receptor blocker (ARB) olmesartan, is predominantly anionic at intestinal pH. Human...
PURPOSE
Olmesartan medoxomil (olmesartan-MX), an ester-type prodrug of the angiotensin II receptor blocker (ARB) olmesartan, is predominantly anionic at intestinal pH. Human organic anion transporting polypeptide 2B1 (OATP2B1) is expressed in the small intestine and is involved in the absorption of various acidic drugs. This study was designed to test the hypothesis that OATP2B1-mediated uptake contributes to the enhanced intestinal absorption of olmesartan-MX, even though olmesartan itself is not a substrate of OATP2B1.
METHODS
Tetracycline-inducible human OATP2B1- and rat Oatp2b1-overexpressing HEK 293 cell lines (hOATP2B1/T-REx-293 and rOatp2b1/T-REx-293, respectively) were established to characterize OATP2B1-mediated uptake. Rat jejunal permeability was measured using Ussing chambers. ARBs were quantified by liquid chromatography-tandem mass spectrometry.
RESULTS
Significant olmesartan-MX uptake was observed in hOATP2B1/T-REx-293 and rOatp2b1/T-REx-293 cells, whereas olmesartan uptake was undetectable or much lower than olmesartan-MX uptake, respectively. Furthermore, olmesartan-MX exhibited several-fold higher uptake in Caco-2 cells and greater permeability in rat jejunum compared to olmesartan. Olmesartan-MX uptake in hOATP2B1/T-REx-293 cells and in Caco-2 cells was significantly decreased by OATP2B1 substrates/inhibitors such as 1 mM estrone-3-sulfate, 100 µM rifamycin SV, and 100 µM fluvastatin. Rat Oatp2b1-mediated uptake and rat jejunal permeability of olmesartan-MX were significantly decreased by 50 µM naringin, an OATP2B1 inhibitor. Oral administration of olmesartan-MX with 50 µM naringin to rats significantly reduced the area under the plasma concentration-time curve of olmesartan to 76.9%.
CONCLUSION
Olmesartan-MX is a substrate for OATP2B1, and the naringin-sensitive transport system contributes to the improved intestinal absorption of olmesartan-MX compared with its parent drug, olmesartan.
Topics: Animals; Humans; Intestinal Absorption; Olmesartan Medoxomil; Prodrugs; HEK293 Cells; Tetrazoles; Organic Anion Transporters; Male; Imidazoles; Rats; Rats, Sprague-Dawley; Jejunum; Angiotensin II Type 1 Receptor Blockers; Permeability; Caco-2 Cells
PubMed: 38485855
DOI: 10.1007/s11095-024-03687-1 -
Saudi Pharmaceutical Journal : SPJ :... Mar 2024This study was designed to assess both the quality and cost aspects of various branded and generic formulations of angiotensin receptor blockers, specifically...
This study was designed to assess both the quality and cost aspects of various branded and generic formulations of angiotensin receptor blockers, specifically Irbesartan, Losartan Potassium, Olmesartan Medoxomil, Telmisartan, and Valsartan. The collected samples underwent distinct quality evaluations using the methods outlined in different global Pharmacopoeias (British Pharmacopoeia/European Pharmacopoeia, Indian Pharmacopoeia and United States Pharmacopoeia). These drugs were characterized using Fourier-Transform Infrared Spectroscopy and Nuclear Magnetic Resonance techniques, while their quality and concentration were analysed using High Performance Liquid Chromatography. The release profile of the drugs was examined through dissolution testing. Additionally, a cost comparison analysis was carried out by determining the prevailing market prices of the drugs. The evaluated branded and generic angiotensin receptor blockers were found to meet the established standards for impurities, active drug content, and dissolution as set by these Pharmacopoeias, indicating their optimal quality. Notably, the generic drugs exhibited significantly lower costs compared to their branded counterparts. This study confirms that the quality of generic angiotensin receptor blockers is equivalent to that of their branded counterparts. Consequently, these findings support the practicality of utilizing generic drugs as a more economically sustainable and cost-effective approach to managing diseases, especially those of chronic nature.
PubMed: 38380162
DOI: 10.1016/j.jsps.2024.101985 -
Experimental and Therapeutic Medicine Feb 2024Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan...
Efficacy and safety of olmesartan medoxomil‑amlodipine besylate tablets (Sevikar) in older patients with essential hypertension: Subgroup analysis from the Sevikar study.
Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablets in older Chinese patients with essential hypertension has not been performed. Therefore, the present study aimed to evaluate the efficacy and safety of OM-AML tablets in these patients. A total of 463 older Chinese patients with essential hypertension treated with OM-AML (20/5 mg) tablets (Sevikar) were analyzed in a prospective, single-arm, multi-center, real-world study. Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, and at week (W)4 and W8 after OM-AML tablet administration were measured. The mean ± standard error change of SeSBP/SeDBP was -10.3±0.8/-4.6±0.5 and -12.5±0.8/-5.6±0.5 mmHg at W4 and W8, respectively. At W4, 74.1 and 26.8% of patients achieved BP target according to the China and American Heart Association (AHA) criteria, while at W8, 78.0 and 38.7% of patients reached these BP targets accordingly. Finally, 76.5 and 80.5% of patients achieved BP response at W4 and W8, respectively. Furthermore, home-measured SeSBP and SeDBP were significantly decreased from W1 to W8 (both P<0.001). Additionally, the satisfaction of both patients and physicians was elevated at W8 compared with at W0 (both P<0.001). The medication possession rate from baseline to W4 and W8 was 95.5 and 92.5%. The most common drug-associated adverse events by system organ classes were nervous system disorder (4.5%), vascular disorder (2.8%), and general disorder and administration site conditions (2.6%), which were generally mild. In conclusion, OM-AML tablets may be considered effective and safe in lowering BP, enabling the achievement of guideline-recommended BP targets in older Chinese patients with essential hypertension.
PubMed: 38234624
DOI: 10.3892/etm.2023.12338 -
Analytical Chemistry Jan 2024In this paper, we demonstrate the existence of an endogenous mitochondrial azoreductase (AzoR) activity that can induce the cleavage of N═N double bonds of azobenzene...
In this paper, we demonstrate the existence of an endogenous mitochondrial azoreductase (AzoR) activity that can induce the cleavage of N═N double bonds of azobenzene compounds under normoxic conditions. To this end, 100% OFF-ON azo-based fluorogenic probes derived from 4-amino-1,8-naphthalimide fluorophores were synthesized and evaluated. The in vitro study conducted with other endogenous reducing agents of the cell, including reductases, demonstrated both the efficacy and the selectivity of the probe for AzoR. Confocal experiments with the probe revealed an AzoR activity in the mitochondria of living cells under normal oxygenation conditions, and we were able to demonstrate that this endogenous AzoR activity appears to be expressed at different levels across different cell lines. This discovery provides crucial information for our understanding of the biochemical processes occurring within the mitochondria. It thus contributes to a better understanding of its function, which is implicated in numerous pathologies.
Topics: Naphthalimides; Amlodipine Besylate, Olmesartan Medoxomil Drug Combination; NADH, NADPH Oxidoreductases; Fluorescent Dyes; Nitroreductases
PubMed: 38230524
DOI: 10.1021/acs.analchem.3c05030 -
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 -
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