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AAPS PharmSciTech Oct 2020During production, the supplemental file "Trajectory analysis of 5ns MD simulation of VA-64 and OLM.mpeg", as well as the "RunNo and Serial numbers", for Table III and...
During production, the supplemental file "Trajectory analysis of 5ns MD simulation of VA-64 and OLM.mpeg", as well as the "RunNo and Serial numbers", for Table III and Table VII respectively, were inadvertently omitted from the published article.
PubMed: 33006687
DOI: 10.1208/s12249-020-01820-y -
AAPS PharmSciTech Sep 2020Olmesartan medoxomil (OLM) an antihypertensive molecule with poor solubility and poor bioavailability (26% when taken orally) was selected as a model drug. Herein,...
Olmesartan medoxomil (OLM) an antihypertensive molecule with poor solubility and poor bioavailability (26% when taken orally) was selected as a model drug. Herein, rationale development of amorphous solid dispersion with hot-melt extrusion of poorly bioavailable OLM was carried out with the aid of quality by design (QbD), in-silico, in-vitro, and in-vivo evaluations. Polymer selection commenced with the selection of thermoplastic water-soluble polymers with the compatible processing temperature window as per the thermal behavior of OLM. Molecular dynamics (MD) simulations as well assisted in the selection of a carrier. Promising dissolution enhancement was observed with the help of Kollidon VA-64 (VA-64) as a carrier. Optimization of the formulation was executed using the QbD approach with design of experiment as a statistical optimization tool. Interactions between VA-64 and OLM on the atomic level were studied with the help of atomistic MD simulations. Characterization of the optimized extrudates were carried out with scanning electron microscopy, atomic force microscopy, differential scanning calorimetry, thermogravimetric analysis, Fourier transforms infrared spectroscopy, powder X-ray diffraction, in-vitro dissolution study, and in-vivo pharmacokinetic studies. Molecular-level mixing of OLM with VA-64 resulted into glass solution formation which rapidly dissolves (28 times in-vitro dissolution enhancement) in GI tract fluids and instantly gets absorbed into blood circulation. In-vivo pharmacokinetic studies performed in Sprague-Dawley rats reflected superior bioavailability (201.60%) with a significant increase in the C with short T through amorphization of OLM. The in-silico results were in agreement with the observed results of in-vitro dissolution studies and in-vivo pharmacokinetic study.
Topics: Administration, Oral; Animals; Antihypertensive Agents; Biological Availability; Calorimetry, Differential Scanning; Computer Simulation; Hot Melt Extrusion Technology; In Vitro Techniques; Olmesartan Medoxomil; Rats; Rats, Sprague-Dawley; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 32888102
DOI: 10.1208/s12249-020-01780-3 -
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 -
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 -
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 -
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 -
Internal Medicine Journal May 2020Duodenal villous atrophy with olmesartan was described in 2012, 10 years following registration of olmesartan. Clinical features are severe watery diarrhoea, usually...
Duodenal villous atrophy with olmesartan was described in 2012, 10 years following registration of olmesartan. Clinical features are severe watery diarrhoea, usually occurring in association with weight loss. Onset is delayed, with a mean duration of prior exposure to olmesartan of 3 years. Diagnosis may be delayed. Symptoms resolve over weeks following cessation of olmesartan. Epidemiological studies suggest increased risk with olmesartan, rather than a class effect of all angiotensin receptor blockers. Post-marketing surveillance for drug safety remains important.
Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Atrophy; Humans; Hypertension; Imidazoles; Olmesartan Medoxomil; Tetrazoles
PubMed: 32431039
DOI: 10.1111/imj.14834 -
Blood Pressure Aug 2020Most guidelines for treatment of hypertension in the setting of diabetes recommend a blood pressure (BP) target of <130/80 mmHg. However, uncertainty exists about the... (Randomized Controlled Trial)
Randomized Controlled Trial
Most guidelines for treatment of hypertension in the setting of diabetes recommend a blood pressure (BP) target of <130/80 mmHg. However, uncertainty exists about the extent, effectiveness and safety of lowering BP in diabetics. To expand the evidence on this issue, we analysed data from the Randomised Olmesartan and Diabetes MicroAlbuminuria Prevention (ROADMAP) study population. Substudy with blood pressure readings.: The response after initiation of therapy and adequacy of BP control across patients with different BP levels at baseline were analysed.: BP at randomisation was 136.2(15.3)/80.6(9.5) [mean (SD)] mmHg with a range of 87-213/37-123 mmHg. At 1 year, mean BP was 127 (11.9)/75 (8.1) mmHg and the overall control rate (<130/80 mmHg) exceeded 61% in this population. The mean reductions in systolic [-9.4 (15.4) mmHg] and diastolic BP [-5.4 (9.5) mmHg] were highly dependent on the BP stage at Visit 1. At 1 year, treatment decreased the prevalence of patients with baseline BP levels of >160/100 from 9 to 2%[[mean BP change -31 (15.7)/ -14 (9.8) mmHg]] and of 140-159/90-99 mmHg from 32 to 11% [[mean BP change -16(12.7)/ -8.9 (8.7) mmHg]], with corresponding increases in the prevalence of patients with baseline BP levels of 120-139/80-99 from 48 to 65% [[mean BP change -4.1 (10.6)/ -3.1 (7.8) mmHg]]and of <120/80 from 11 to 22% [[mean BP change +5.9 (11.8)/+2.5 (8.6) mmHg]]. These effects did not change significantly thereafter and were maintained throughout follow-up.: Blood pressure control is feasible in patients with diabetes without nephropathy, independent of baseline BP values. Asymmetric BP-lowering in the first year after starting therapy represents a true antihypertensive effect with sustainable shifts in BP severity.
Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Diabetes Mellitus; Double-Blind Method; Europe; Female; Humans; Hypertension; Male; Olmesartan Medoxomil; Time Factors; Treatment Outcome
PubMed: 32279529
DOI: 10.1080/08037051.2020.1750298 -
Drug Development and Industrial Pharmacy May 2020This study aims to detect the enhancement in the oral bioavailability of a poorly water-soluble antihypertensive drug Olmesartan Medoxomil (OM) due to the formulation...
This study aims to detect the enhancement in the oral bioavailability of a poorly water-soluble antihypertensive drug Olmesartan Medoxomil (OM) due to the formulation of lyophilized oily-core nanocapsules. A comparative pharmacokinetic study in rats was conducted for oily-core polymeric nanocapsules (ONC) after formulation and lyophilization against market tablet products to show the significant improvement in oral absorption of OM. OM loaded ONC were prepared using poly-Ɛ-caprolactone (0.5% w/v) as a polymer and an oily core of Labrafac PG by applying a well-controlled nanoprecipitation technique in terms of injection rate (80 mL/h) and magnetic stirring rate (300 rpm). The prepared lyophilized ONC were characterized after reconstitution and evaluated for oral bioavailability after a single OM oral dose (20 mg/kg) of reconstituted lyophilized ONC dispersion was administered to rats. The prepared lyophilized ONC containing 10% w/v mannitol showed an average particle size of 158 nm, polydispersity index of 0.37, negative zeta potential value equals 33.9 and entrapment efficiency of 90%. The dissolution profile for OM from lyophilized ONC powder filled into hard gelatin capsules (HGC) showed a 1.8-fold increase in dissolution rate as compared to the pure drug. pharmacokinetic study in rats revealed a significant enhancement in the oral bioavailability of OM with 1.6-fold increase for AUC and a 1.9-fold increase for as compared to marketed product. It is concluded that the formulation of lyophilized ONC for OM can significantly enhance its oral bioavailability and consequently, its therapeutic efficacy and patient compliance.
Topics: Administration, Oral; Animals; Biological Availability; Caproates; Drug Compounding; Freeze Drying; Lactones; Male; Nanocapsules; Oils; Olmesartan Medoxomil; Rats; Rats, Wistar
PubMed: 32275456
DOI: 10.1080/03639045.2020.1753763 -
Blood Pressure Apr 2020
How to deal with the occurrence of rare drug-induced adverse events: the example of sprue-like enteropathy induced by olmesartan medoxomil and other angiotensin-receptor blockers.
Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Celiac Disease; Humans; Hypertension; Incidence; Olmesartan Medoxomil; Patient Safety; Risk Assessment; Risk Factors
PubMed: 32049554
DOI: 10.1080/08037051.2020.1726101