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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 -
Spectrochimica Acta. Part A, Molecular... Jun 2023For the first time a spectrofluorimetric method had been achieved for the concurrent analysis of metoprolol succinate (MET) and olmesartan medoxomil (OLM). The approach...
Coupling of synchronous fluorescence spectroscopy with derivative amplitude outcomes for simultaneous determination of metoprolol succinate and olmesartan medoxomil in combined pharmaceutical preparation: Application in spiked human plasma.
For the first time a spectrofluorimetric method had been achieved for the concurrent analysis of metoprolol succinate (MET) and olmesartan medoxomil (OLM). The approach depended on assessing the first order derivative (D) of the synchronous fluorescence intensity of the two drugs in aqueous solution at Δλ of 100 nm. The amplitudes of D at 300 nm and 347 nm were measured for MET and OLM, respectively. The linearity ranges were 100-1000 ng/mL and 100-5000 ng/mL for OLM and MET, respectively. This approach is uncomplicated, repetitive, quick, and affordable. The results of analysis had been statistically verified. The validation assessments were carried out following the recommendations of The International Council for Harmonization (ICH). This technique could be employed to assess marketed formulation. The method was sensitive with limits of detection (LOD) of 32 ng/ml and 14 ng/mL for MET and OLM, respectively. Limits of quantitation (LOQ) were 99 ng/ml for MET and 44 ng/mL for OLM. So it can be applied to determine both drugs in spiked human plasma within the linearity ranges of 100-1000 ng/mL for OLM and 100-1500 ng/mL for MET.
Topics: Humans; Olmesartan Medoxomil; Metoprolol; Spectrometry, Fluorescence; Pharmaceutical Preparations
PubMed: 36863080
DOI: 10.1016/j.saa.2023.122549 -
Drug Design, Development and Therapy 2019Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) and also a major cause of end-stage renal disease (ESRD). Olmesartan medoxomil (OM) is an...
BACKGROUND
Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) and also a major cause of end-stage renal disease (ESRD). Olmesartan medoxomil (OM) is an angiotensin II receptor blocker (ARB) and has been shown to exhibit renoprotective effects on a streptozotocin (STZ)-induced diabetic rat model. Yet, whether OM affects DN progression and renal injury in db/db mice, a type 2 diabetic murine model, has not been established.
METHODS
Wild-type (n = 15) and db/db mice (n = 15) were treated with control saline or OM via oral gavage. The physiological and biochemical parameters were evaluated and histological examinations of kidney specimens were performed.
RESULTS
Compared with saline-treated db/db mice, db/db mice administered with OM showed ameliorated diabetic physiological and biochemical parameters. In addition, OM decreased urinary albumin excretion and plasma creatinine level in db/db mice. Moreover, histologically, OM reduced glomerular hypertrophy and injury, and also ameliorated tubular injury, thus suggesting that OM improves renal function and minimizes renal pathological deterioration in db/db mice.
CONCLUSION
Our study reveals a beneficial role of OM in ameliorating DN in db/db mice, which is associated with its renoprotective function.
Topics: Albuminuria; Angiotensin II Type 1 Receptor Blockers; Animals; Creatinine; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Male; Mice; Olmesartan Medoxomil
PubMed: 31695333
DOI: 10.2147/DDDT.S217826 -
Spectrochimica Acta. Part A, Molecular... Feb 2022For determination of amlodipine besylate (AML) and olmesartan medoxomil (OLM) at the same time, four UV chemometric spectrophotometric techniques were created and tested...
For determination of amlodipine besylate (AML) and olmesartan medoxomil (OLM) at the same time, four UV chemometric spectrophotometric techniques were created and tested in accordance with ICH standards. Method (I) was absorption subtraction method (ASM) using two wavelengths, one of which was of AML at 365 nm and the other was the isoabsorptive point of both drugs at 237 nm. Method (II) was ratio subtraction method (RSM) for determination of OLM at λ = 254 nm by taking the ratio spectrum and subtracting the constant values using 10 μg/mL of AML as a divisor in combination with extended ratio subtraction method (ERSM) to determine AML at λ = 239 nm using 10 μg/mL OLM as a divisor. Method (III) was dual wavelength method; the wavelengths used to determine OLM were 221 nm and 235 nm, while those used to determine AML were 246 nm and 259 nm. Method (IV) was the second order derivative (D) spectrophotometric method at 219 nm for OLM and 227 nm for AML. The proposed approaches were used to achieve linearity in the concentration range of 2-25 μg/mL for both drugs. The approaches were found to be uncomplicated, reproducible, efficient, and cost-effective as well as they were successfully used to determine the cited drugs in both laboratory samples and commercial pharmaceutical formulations.
Topics: Amlodipine; Olmesartan Medoxomil; Spectrophotometry; Tablets
PubMed: 34624815
DOI: 10.1016/j.saa.2021.120455 -
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 -
Biomedical Chromatography : BMC Nov 2021The current work describes the development and validation of a stability-indicating UPLC method for the determination of olmesaratan medoxomil (OLM), amlodipine besylate...
Development and validation of a stability-indicating UPLC method for the determination of olmesartan medoxomil, amlodipine and hydrochlorothiazide degradation impurities in their triple-combination dosage form using factorial design of experiments.
The current work describes the development and validation of a stability-indicating UPLC method for the determination of olmesaratan medoxomil (OLM), amlodipine besylate (AMB), hydrochlorothiazide (HCT) and their degradation products in the triple-combination tablet dosage form. The separation was achieved using a Zorbax Eclipse plus C RRHD (100 mm × 3.0 mm), 1.8 μm column with gradient elution of mobile phase A containing 0.02 m of sodium phosphate buffer (pH 3.35) and mobile phase B as acetonitrile and water (90:10, v/v). The detector signal was monitored at UV 250 nm. Analytical performance of the optimized UPLC method was validated as per International Conference on Harmonization guidelines. The linearity ranges for OLM, AMB and HCT were 0.59-240, 0.30-60 and 0.37-150 μg/ml, respectively, with correlation coefficients >0.999. The dosage form was subjected to forced-degradation conditions of neutral, acidic and alkaline hydrolysis, oxidation and thermal and photodegradation. The method was proved to be stability indicating by demonstrating the specificity of the drugs from degradation products. The robustness of the method was evaluated through a two-level, three-factorial design with a multivariate approach. Statistical data analysis with best model fit P-value < 0.05 from an ANOVA test indicated that the influence of individual factors is relatively higher than the interaction effects. The method is useful for the analysis of drug products.
Topics: Amlodipine; Chromatography, High Pressure Liquid; Drug Contamination; Drug Stability; Hydrochlorothiazide; Limit of Detection; Linear Models; Olmesartan Medoxomil; Reproducibility of Results; Research Design; Tablets
PubMed: 34110035
DOI: 10.1002/bmc.5194 -
High Blood Pressure & Cardiovascular... Mar 2023Blood pressure control remains an unmet clinical need. Only about half of patients achieve their blood pressure (BP) targets and of these, the majority require... (Review)
Review
Blood pressure control remains an unmet clinical need. Only about half of patients achieve their blood pressure (BP) targets and of these, the majority require combination and double or triple therapies. International guidelines recommend the association of drugs with complementary mechanisms of action and, in particular, the combination of renin-angiotensin system (RAS) inhibitors, calcium channel blockers (CCBs), and diuretics. Among the various angiotensin receptor blockers, olmesartan (OM) is available as a monotherapy and in dual and triple single-pill combinations (SPCs) with amlodipine (AML) and/or hydrochlorothiazide (HCTZ). Several phase III and IV studies, together with real-world studies, have demonstrated the additional benefits of combining OM either with AML or with HCTZ in terms of BP control and target BP achievements both in the general population and in special subgroups of hypertensive patients, such as the elderly, diabetic, chronic kidney disease or obese patients. Ambulatory BP monitoring studies assessing 24h BP have also demonstrated that dual, as well as triple, OM-based SPCs induce a more sustained and smoother BP reduction than placebo and monotherapy. Furthermore, triple OM-based SPC has been shown to improve therapeutic adherence in hypertensive patients compared to free combinations. The availability of OM combined with HCTZ, AML or both at different dosages makes it a valuable option to customize therapy based on the levels of BP and the clinical characteristics of hypertensive patients.
Topics: Humans; Aged; Antihypertensive Agents; Blood Pressure; Olmesartan Medoxomil; Drug Therapy, Combination; Hypertension; Amlodipine; Hydrochlorothiazide; Leukemia, Myeloid, Acute
PubMed: 36696054
DOI: 10.1007/s40292-023-00563-8 -
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 -
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 -
Cureus Jul 2023Olmesartan is a commonly used antihypertensive medication belonging to the class of angiotensin II receptor blockers. Though generally well-tolerated, olmesartan can...
Olmesartan is a commonly used antihypertensive medication belonging to the class of angiotensin II receptor blockers. Though generally well-tolerated, olmesartan can rarely cause olmesartan-associated enteropathy (OAE) with non-bloody diarrhea, weight loss, abdominal pain, and vomiting. Patients may develop enteropathy months to years after drug initiation. In severe cases, patients may develop complications that require hospitalization. Diagnosis is often delayed due to unfamiliarity of OAE, nonspecific presenting symptoms, and normal-appearing gross endoscopic findings. Esophagogastroduodenoscopy (EGD) with biopsy is essential to the diagnosis, showing sprue-like enteropathy with intestinal villous atrophy and mucosal inflammation. This report describes a case of a 70-year-old man who presented with three months of profuse watery diarrhea and 40-pound unintentional weight loss. After an extensive workup, including EGD with duodenal biopsies, the patient was diagnosed with OAE. The biopsies showed findings consistent with acute and chronic duodenitis, mucosal desquamation and ulceration, blunting of villi, and a sprue-like pattern with neutrophils. Celiac serologies and anti-enterocyte antibodies were negative, further supporting the diagnosis of OAE. Complete resolution of symptoms was achieved by discontinuing olmesartan and administering a steroid taper. Considering the frequent use of olmesartan, the increasing occurrence of OAE, and the wide range of associated symptoms, it is crucial for providers to recognize OAE and consider early discontinuation of olmesartan. This approach can help prevent further intestinal damage, protracted symptoms, unnecessary diagnostic tests, and financial burdens on both patients and the healthcare system.
PubMed: 37559845
DOI: 10.7759/cureus.41604