-
Computational and Mathematical Methods... 2021Ischemic stroke combined with hypertension can increase risks of stroke recurrence and death.
The Clinical Efficacy of Clopidogrel Bisulfate Tablets Combined with Olmesartan Medoxomil for Ischemic Stroke with Hypertension and the Effect of Angiotensin II Type 1 Receptor Level on Prognosis.
BACKGROUND
Ischemic stroke combined with hypertension can increase risks of stroke recurrence and death.
AIM
The aim of this study is to investigate the clinical efficacy of clopidogrel bisulfate tablets combined with olmesartan medoxomil in the treatment of ischemic stroke patients with hypertension and the effect of angiotensin II type 1 receptor (ATR) level on prognosis.
METHODS
Ninety ischemic stroke patients with hypertension were chosen for continuous treatment with clopidogrel bisulfate tablets and olmesartan medoxomil for 12 months. The Modified Edinburgh Scandinavian Stroke Scale (MESSS) score, Brunnstrom score, Barthel score, death, recurrence, and progression of cerebrovascular residual lesions were observed and recorded during the treatment period. According to the plasma ATR expression of the patients before treatment, the patients were divided into a high-ATR group and low-ATR group. Then, survival analysis was performed.
RESULTS
Compared with pretreatment, the MESSS scores of the patients at the first, second, third, sixth, ninth, and twelfth months after treatment were reduced ( < 0.01) while the Brunnstrom score and Barthel score were prominently boosted ( < 0.01). Compared with the low-ATR group, patients in the high-ATR group had higher rates of stroke recurrence and progression of residual cerebrovascular lesions ( < 0.05).
CONCLUSION
Clopidogrel bisulfate tablets combined with olmesartan medoxomil has prominent clinical effects in the treatment of ischemic stroke patients with hypertension, evidently improving the prognosis. In addition, the level of ATR may be a vital factor affecting the prognosis.
Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Clopidogrel; Computational Biology; Drug Therapy, Combination; Female; Humans; Hypertension; Ischemic Stroke; Male; Middle Aged; Olmesartan Medoxomil; Platelet Aggregation Inhibitors; Prognosis; Receptor, Angiotensin, Type 1; Treatment Outcome
PubMed: 34745325
DOI: 10.1155/2021/4487393 -
Polymers Jul 2021Olmesartan medoxomil (OLM) is one of the prominent antihypertensive drug that suffers from low aqueous solubility and dissolution rate leading to its low...
Olmesartan medoxomil (OLM) is one of the prominent antihypertensive drug that suffers from low aqueous solubility and dissolution rate leading to its low bioavailability. To improve the oral bioavailability of OLM, a delivery system based on ethylcellulose (EC, a biobased polymer) nanosponges (NSs) was developed and evaluated for cytotoxicity against the A549 lung cell lines and antihypertensive potential in a rat model. Four OLM-loaded NSs (ONS1-ONS4) were prepared and fully evaluated in terms of physicochemical properties. Among these formulations, ONS4 was regarded as the optimized formulation with particle size (487 nm), PDI (0.386), zeta potential (ζP = -18.1 mV), entrapment efficiency (EE = 91.2%) and drug loading (DL = 0.88%). In addition, a nanosized porous morphology was detected for this optimized system with NS surface area of about 63.512 m/g, pore volume and pore radius Dv(r) of 0.149 cc/g and 15.274 Å, respectively, measured by nitrogen adsorption/desorption analysis. The observed morphology plus sustained release rate of OLM caused that the optimized formulation showed higher cytotoxicity against A549 lung cell lines in comparison to the pure OLM. Finally, this system (ONS4) reduced the systolic blood pressure (SBP) significantly ( < 0.01) as compared to control and pure OLM drug in spontaneously hypertensive rats. Overall, this study provides a scientific basis for future studies on the encapsulation efficiency of NSs as promising drug carriers for overcoming pharmacokinetic limitations.
PubMed: 34301030
DOI: 10.3390/polym13142272 -
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 -
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 -
Journal of Clinical Hypertension... May 2021Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more... (Meta-Analysis)
Meta-Analysis
Is the newest angiotensin-receptor blocker azilsartan medoxomil more efficacious in lowering blood pressure than the older ones? A systematic review and network meta-analysis.
Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more effective than the older ones. A network meta-analysis was performed to compare the efficacy of various angiotensin-receptor blockers in reducing office and ambulatory blood pressure in hypertensive patients. Relevant literature was searched from English and Chinese databases for randomized controlled trials involving angiotensin-receptor blockers in hypertension. Efficacy variables included systolic and diastolic blood pressure either in the office or on ambulatory blood pressure monitoring. Absolute blood pressure reductions at 6-12 weeks of treatment and their credible intervals were reported. A total of 34 publications provided adequate data for analysis (n = 14 859). In 28 studies on office systolic blood pressure (n = 12 731), against the common comparator valsartan 80 mg, the differences in systolic blood pressure were in favor of azilsartan medoxomil (20-80 mg), irbesartan (300 mg), olmesartan (20-40 mg), telmisartan (80 mg), and valsartan (160-320 mg), but not candesartan (8-16 mg), losartan (50-100 mg), irbesartan (150 mg), olmesartan (10 mg), and telmisartan (40 mg). The ranking plot shows that azilsartan medoxomil 80 mg had a possibility of 99% being the best in the class. Similar results were observed for office diastolic blood pressure and from 13 studies for 24-hour ambulatory systolic and diastolic blood pressure. In conclusion, angiotensin-receptor blockers had different blood pressure lowering efficacy. The newest angiotensin-receptor blocker azilsartan medoxomil at the dose of 80 mg seemed to be most efficacious in reducing both systolic and diastolic blood pressure in the office and on ambulatory measurement.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensins; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Humans; Hypertension; Network Meta-Analysis; Olmesartan Medoxomil; Oxadiazoles; Tetrazoles
PubMed: 33609077
DOI: 10.1111/jch.14227 -
Gastroenterology Research Aug 2020Olmesartan is an angiotensin II receptor blocker (ARB) drug approved in 2002 for the treatment of hypertension. Since 2012, there have been reports of a rare adverse...
Olmesartan is an angiotensin II receptor blocker (ARB) drug approved in 2002 for the treatment of hypertension. Since 2012, there have been reports of a rare adverse effect suspected to be related to its use. The author presents a case of a 63-year-old female with refractory gastrointestinal (GI) symptoms including diarrhea with associated weight loss and severe electrolyte abnormalities necessitating hospitalization. An extensive inpatient evaluation ensued and was initially unremarkable. Esophagogastroduodenoscopy (EGD) discovered an endoscopically normal duodenum that was biopsied and notably revealed villous atrophy and intraepithelial lymphocytosis. Colonoscopy was normal appearing though biopsy findings were significant for nonspecific colitis. The endoscopy findings in the setting of the clinical presentation confirmed the diagnosis of olmesartan-associated enteropathy (OAE). Clinical improvement was noted after cessation of olmesartan and histological resolution was confirmed with repeat EGD post-discharge.
PubMed: 32864026
DOI: 10.14740/gr1301 -
Advanced Pharmaceutical Bulletin Jul 2020The present work endeavors to report a systematic approach of developing the lipidic self-nanoemulsifying formulation of olmesartan medoxomil (OMT) on the principles of...
The present work endeavors to report a systematic approach of developing the lipidic self-nanoemulsifying formulation of olmesartan medoxomil (OMT) on the principles of Quality by Design (QbD). For preparing the self-nanoemulsifying formulation, a mixture of oil, surfactant and cosurfactant were used as vehicles. The excipients were selected after screening by solubility as well as pseudoternary phase titration studies. Mixture design was adopted for systematic optimization of the composition of nanolipidic formulations, which were evaluated for smaller globule size, stable zeta potential and lower values of polydispersity index. The optimized liquid self-nanoemulsifying formulation was identified using numerical and graphical optimization techniques, followed by validation of the experimental model. Solidification of self-nanoemulsifying formulation was carried out using porous carriers, and then optimized on the basis of oil adsorption potential, powder flow property and drug release performance. Pharmacokinetic study was performed in male Wistar rats for evaluating the drug absorption parameters. All the experimental data obtained were subjected to statistical analysis using oneway ANOVA followed by post hoc analysis using Student's t test. The optimized liquid self-nanoemulsifying formulation showed globule size <100 nm, emulsification efficiency <5 minutes and drug release >85% within in 30 minutes. Further, the solid SNEDDS formulation was effectively formulated using Neusilin US2 with maximum oil adsorption capacity and good micromeritic properties. Pharmacokinetic evaluation indicated 4 to 5-folds increase ( <0.05) in the values of C, AUC, and reduction in T from the nanoformulations vis-à-vis the marketed formulation. Overall, the developed nanolipidic formulation of olmesartan indicated superior efficacy in augmenting the drug dissolution and absorption performance.
PubMed: 32665896
DOI: 10.34172/apb.2020.046 -
BMC Pharmacology & Toxicology Jan 2020Sodium-glucose cotransporter 2 (SGLT2) inhibitors inhibit SGLT2, which is expressed in the proximal renal tubule, and thus reduce blood glucose levels by enabling the...
BACKGROUND
Sodium-glucose cotransporter 2 (SGLT2) inhibitors inhibit SGLT2, which is expressed in the proximal renal tubule, and thus reduce blood glucose levels by enabling the urinary excretion of excess glucose. SGLT2 inhibitors have been reported to suppress the complications of diabetes and reduce overall mortality. However, little is known about the types of symptoms that may occur in response to an overdose of an SGLT2 inhibitor. Here, we describe a case of intoxication caused by an overdose of an SGLT2 inhibitor.
CASE PRESENTATION
An otherwise physically healthy adult woman ingested an overdose of ipragliflozin, an SGLT2 inhibitor, and a polypill of olmesartan medoxomil, and azelnidipine in a suicide attempt. Although her blood ipragliflozin concentration was very high (9516.3 ng/mL) upon hospital arrival, her initial blood glucose level was normal, and she did not exhibit symptoms such as hypoglycemia or polyuria. Moderate renal dysfunction associated with an estimated glomerular filtration rate of 42.3 mL/min/1.73 m was observed. Thirty-six hours after ingestion, her blood ipragliflozin concentration decreased to a level equivalent to that observed after a therapeutic dose and her renal function improved almost simultaneously. After improvement in her renal function, the osmotic diuretic effect of the drug progressed. Her blood glucose level declined slightly but was in the normal range due to glucose administration. During the clinical course, fatal hypoglycemia was not observed.
CONCLUSIONS
Our case showed that an overdose of an SGLT2 inhibitor caused toxic effects on renal function, but severe hypoglycemia was not observed. Additional cases of intoxication from SGLT2 inhibitors alone would be helpful to clarify the mechanism of intoxication.
Topics: Adult; Drug Overdose; Female; Glucosides; Humans; Hypotension; Kidney; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes
PubMed: 31918741
DOI: 10.1186/s40360-019-0381-z -
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 -
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