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Journal of the American Heart... 2014The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study showed that 40 mg Olmesartan medoxomil (OM) versus placebo delayed microalbuminuria... (Observational Study)
Observational Study Randomized Controlled Trial
The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) observational follow-up study: benefits of RAS blockade with olmesartan treatment are sustained after study discontinuation.
BACKGROUND
The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study showed that 40 mg Olmesartan medoxomil (OM) versus placebo delayed microalbuminuria onset in patients with type 2 diabetes and normoalbuminuria.
METHODS AND RESULTS
One thousand seven hundred and fifty-eight ROADMAP patients (placebo arm: 877; OM arm: 881) participated in the observational follow up (OFU) with an average of 3.3 years. They received standard medical care and micro- and macrovascular events were documented. During observational follow-up 62.9% and 60.1% in the former OM and placebo group, respectively, received treatment with a RAS blocking agent. During the OFU period the systolic blood pressure (SBP) increased to mean values of 135 mm Hg in both groups. Patients who had developed microalbuminuria during ROADMAP had a higher incidence of cardio- and cerebrovascular events (OR 1.77, CI 1.03 to 3.03, P=0.039) during the OFU period compared with patients in whom this was not the case. Diabetic retinopathy was significantly reduced in the former OM group (8 [0.9%] versus 23 [2.6%], OR: 0.34, CI 0.15 to 0.78, P=0.011) and the rate of microalbuminuria was numerically reduced. Congestive heart failure requiring hospitalization (3 [0.3%] versus 12 [1.4%], OR: 0.23, CI 0.06 to 0.85, P=0.027) was reduced and there was a trend of reduced cardio-/cerebrovascular events (OM versus Pb: 73 [8.3%] versus 86 [9.8%] patients). Seven (0.8%) deaths (including 2 CV events) were reported in former placebo patients versus 3 (0.3%) (non-CV events) in former OM patients.
CONCLUSIONS
Development of microalbuminuria is a valid marker for future CV events. RAS blockade with Olmesartan might cause sustained reduction (legacy effect) of micro- and macrovascular events.
Topics: Aged; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Female; Follow-Up Studies; Humans; Imidazoles; Kidney; Logistic Models; Male; Middle Aged; Odds Ratio; Olmesartan Medoxomil; Proportional Hazards Models; Renin-Angiotensin System; Risk Assessment; Risk Factors; Tetrazoles; Time Factors; Treatment Outcome
PubMed: 24772521
DOI: 10.1161/jaha.114.000810 -
Drug Metabolism and Pharmacokinetics 2009The objectives of this study were to identify the factors influencing antihypertensive response to the angiotensin receptor blocker, olmesartan medoxomil, or the calcium... (Randomized Controlled Trial)
Randomized Controlled Trial
The objectives of this study were to identify the factors influencing antihypertensive response to the angiotensin receptor blocker, olmesartan medoxomil, or the calcium channel blocker, azelnidipine, and to discuss the possibility of utilizing them as predictors for drug selection prior to therapy. A two-way crossover study of olmesartan medoxomil and azelnidipine was conducted in 29 patients with mild to moderate essential hypertension. The 24-hour ambulatory blood pressure measurements (ABPM) and plasma drug concentrations were obtained on the first and at the end of each treatment period, and were analyzed using population pharmacokinetic/pharmacodynamic (PK/PD) modeling approach. The population PK/PD models considering circadian variations in baseline blood pressure well described the observed plasma drug concentrations and 24-hour ABPM profiles. Pre-treatment plasma renin activity (PRA) was identified as a significant covariate on the maximum drug effect (E(max)) of olmesartan, whereas azelnidpine E(max) was independent of patient background characteristics investigated. No patient was found to have a high E(max) to one agent who also had a high E(max) to the other. In conclusion, the effects of olmesartan medoxomil and azelnidipine were modestly correlated with pharmacokinetic profiles, and the pre-treatment PRA level could be a useful determinant of responsiveness in selecting olmesartan medoxomil and azelnidipine.
Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Azetidinecarboxylic Acid; Blood Pressure; Calcium Channel Blockers; Circadian Rhythm; Clinical Laboratory Techniques; Cross-Over Studies; Dihydropyridines; Female; Humans; Hypertension; Imidazoles; Individuation; Male; Middle Aged; Olmesartan Medoxomil; Population Groups; Tetrazoles
PubMed: 19745564
DOI: 10.2133/dmpk.24.376 -
Vascular Health and Risk Management 2009Guidelines recommend blood pressure (BP) in hypertensive patients should be <140 systolic BP (SBP) and <90 diastolic BP (DBP) mmHg. This analysis assessed goal rate... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Guidelines recommend blood pressure (BP) in hypertensive patients should be <140 systolic BP (SBP) and <90 diastolic BP (DBP) mmHg. This analysis assessed goal rate achievement in hypertensive patients receiving olmesartan-based treatment in the OLMEBEST study.
METHODS
Patients with essential hypertension (DBP > or = 90 mmHg and <110 mmHg) received open-label olmesartan medoxomil 20 mg/day (n = 2306). After 8 weeks, patients with DBP > or = 90 mmHg (n = 627) were randomized to 4 weeks' double-blind treatment with olmesartan 40 mg/day monotherapy or olmesartan 20 mg/day plus hydrochlorothiazide (HCTZ) 12.5 mg/day. For this analysis, the numbers and proportions of patients who achieved SBP < 140 mmHg and/or DBP < 90 mmHg at the end of the 4 weeks were calculated.
RESULTS
In patients who achieved DBP normalization (<90 mmHg) at week 8 (n = 1546) and continued open-label olmesartan 20 mg/day, 66.7% achieved SBP/DBP < 140/90 mmHg at Week 12. In patients who did not achieve DBP normalization at Week 8, 26.8% of those randomized to olmesartan 40 mg/day and 42.5% of those randomized to olmesartan 20 mg/day plus HCTZ 12.5 mg/day achieved a SBP/DBP < 140/90 mmHg at Week 12.
CONCLUSION
Olmesartan 40 mg/day and olmesartan 20 mg/day plus HCTZ 12.5 mg/day allow substantial proportions of patients to achieve BP goals.
Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Diuretics; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Middle Aged; Olmesartan Medoxomil; Practice Guidelines as Topic; Prospective Studies; Tetrazoles; Time Factors; Treatment Outcome
PubMed: 19756164
DOI: 10.2147/vhrm.s7003 -
Chromatographia Jun 2009Two new, rapid, precise, accurate and specific chromatographic methods were described for the simultaneous determination of olmesartan medoxomil and hydrochlorothiazide...
Two new, rapid, precise, accurate and specific chromatographic methods were described for the simultaneous determination of olmesartan medoxomil and hydrochlorothiazide in combined tablet dosage forms. The first method was based on reversed phase liquid chromatography using an Eurosphere 100 RP C18 column (250 x 4.6 mm ID, 5 mum). The mobile phase was methanol-0.05% o-phosphoric acid (60:40 v/v) at a flow rate of 1.0 mL min(-1). Commercially available tablets and laboratory mixtures containing both drugs were assayed and detected using a UV detector at 270 nm. The second method involved silica gel 60 F(254) high performance thin layer chromatography and densitometric detection at 254 nm using acetonitrile-ethyl acetate-glacial acid (7:3:0.4 v/v/v) as the mobile phase. Calibration curves ranged between 200-600 and 125-375 ng spot(-1) for olmesartan and hydrochlorothiazide, respectively.
PubMed: 19568313
DOI: 10.1365/s10337-009-1094-z -
Journal of Clinical Hypertension... Sep 2009J Clin Hypertens (Greenwich). 2009;11:475-482. (c) 2009 Wiley Periodicals, Inc.The authors report on the 44-week open-label extension of the 8-week, double-blind... (Randomized Controlled Trial)
Randomized Controlled Trial
J Clin Hypertens (Greenwich). 2009;11:475-482. (c) 2009 Wiley Periodicals, Inc.The authors report on the 44-week open-label extension of the 8-week, double-blind Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial in 1684 patients. Initial therapy was amlodipine (AML) plus olmesartan medoxomil (OM) 5+40 mg/d, up-titrated to AML+OM 10+40 mg/d plus hydrochlorothiazide (HCTZ) 12.5 mg then 25 mg if patients did not achieve blood pressure (BP) goal (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes). Baseline mean BP decreased from 164/102 mm Hg to 131/82 mm Hg at end of study, with an overall 66.7% of patients, including those with diabetes, achieving BP goal. The BP goal achievement was 80% for AML+OM 5+40 mg/d, 70.6% for AML+OM 10+40 mg/d, 66.6% for AML+OM+HCTZ 10+40+12.5 mg/d, and 46.3% for AML+OM+HCTZ 10+40+25 mg/d. Study medication was safe and well tolerated. Combination antihypertensive therapy with AML+OM+/-HTCZ, up-titrated as necessary, allowed a majority of patients to achieve BP goal.
Topics: Aged; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diuretics; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Imidazoles; Male; Middle Aged; Multivariate Analysis; Olmesartan Medoxomil; Risk Factors; Tetrazoles; Time Factors
PubMed: 19751459
DOI: 10.1111/j.1751-7176.2009.00159.x -
Current Therapeutic Research, Clinical... Dec 2014Olmesartan is an angiotensin II receptor antagonist and is effective and well tolerated in the treatment of arterial hypertension. Probenecid is a well-established...
BACKGROUND
Olmesartan is an angiotensin II receptor antagonist and is effective and well tolerated in the treatment of arterial hypertension. Probenecid is a well-established hypouricemic agent for the treatment of hyperuricemia and gout.
OBJECTIVE
The goal of this study was to examine the impact of coadministration of probenecid on the pharmacokinetic parameters and tolerability of olmesartan in healthy volunteers.
METHODS
In a randomized, open-label, 2-way crossover study, 12 volunteers received 2 oral treatments (olmesartan alone or olmesartan plus probenecid) separated by 4 days. Blood samples were obtained for a 48-hour pharmacokinetic evaluation after drug administration. Tolerability was assessed by monitoring vital signs and laboratory tests before and after administration of the study drug.
RESULTS
Pharmacokinetic parameters were evaluated in 6 male and 6 female healthy volunteers (mean age, 22 [range, 20-25] years]; weight, 56.0 [range, 51.0-60.0] kg). Probenecid coadministration increased olmesartan Css-av, AUC0→∞, and AUC0-48 by 40%, 50%, and 50%, respectively (P = 0.018, 0.000, 0.000, respectively), but there was no statistical significance for Tmax, t1/2, Css-max, and Css-min between olmesartan plus probenecid and olmesartan alone (P = 0.697, 0.053, 0.521, and 0.734, respectively). No serious adverse event (AE) was reported during the study. The proportion of volunteers with AEs in the olmesartan plus probenecid period (5 of 12 [42%]) was higher than that in the olmesartan-alone period (1 of 12 [8%]). All of the AEs during the olmesartan plus probenecid period were abnormal routine urine test results. The AE in olmesartan-alone period was dizziness. All AEs were classified as mild and considered to be at least possibly related to treatment. All volunteers recovered from the AEs by 2 weeks after the end of the study.
CONCLUSIONS
Probenecid increases the exposure speed of olmesartan by increasing the AUC0-48, AUC0→∞, and Css-av. The combined treatment of olmesartan medoxomil with probenecid may increase the occurrence of genitourinary side effects. ClinicalTrials.gov identifier: NCT01907373.
PubMed: 25067982
DOI: 10.1016/j.curtheres.2013.11.004 -
Journal of Human Hypertension Dec 2010A prespecified subgroup analysis of a 44-week open-label extension study is presented. The efficacy and safety of the combination of amlodipine (AML) + olmesartan... (Randomized Controlled Trial)
Randomized Controlled Trial
Long-term efficacy of a combination of amlodipine and olmesartan medoxomil ± hydrochlorothiazide in patients with hypertension stratified by age, race and diabetes status: a substudy of the COACH trial.
A prespecified subgroup analysis of a 44-week open-label extension study is presented. The efficacy and safety of the combination of amlodipine (AML) + olmesartan medoxomil (OM), with and without the addition of hydrochlorothiazide (HCTZ), were investigated in patients aged ≥65 and <65 years, Blacks and non-Blacks and patients with and without type 2 diabetes. After an 8-week double-blind, placebo-controlled portion of the study, patients initiated therapy on AML 5 + OM 40 mg per day, were uptitrated stepwise to AML 10 + OM 40 mg per day, with the addition of HCTZ 12.5 mg, and 25 mg if blood pressure (BP) goal was not achieved (<140/90 or <130/80 mm Hg for patients with diabetes). Endpoints included the change from baseline in mean seated systolic BP, mean seated diastolic BP and achievement of BP goal. BP decreased from baseline for all treatments in each prespecified subgroup. By the end of the study, BP goal was achieved in 61.0% of patients aged ≥65 years, 68.1% of patients aged <65 years, 63.3% of Blacks, 67.8% of non-Blacks, 26.9% of patients with diabetes and 72.9% of patients without diabetes. The combination of AML + OM ± HCTZ was efficacious, safe and well tolerated by these subgroups.
Topics: Age Factors; Aged; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diuretics; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Middle Aged; Olmesartan Medoxomil; Placebo Effect; Racial Groups; Tetrazoles; Time Factors; Treatment Outcome; United States
PubMed: 20200547
DOI: 10.1038/jhh.2010.16 -
European Journal of Pharmacology Jul 2008Insulin resistance is a major pathological condition associated with obesity and metabolic syndrome. Insulin resistance and the renin-angiotensin system are intimately...
Insulin resistance is a major pathological condition associated with obesity and metabolic syndrome. Insulin resistance and the renin-angiotensin system are intimately linked. We evaluated the role of the renin-angiotensin system in the pathogenesis of insulin resistance-associated, non-alcoholic steatohepatitis by using the angiotensin II type 1 receptor blocker olmesartan medoxomil in a diabetic rat model. The effects of olmesartan on methionine- and choline-deficient (MCD) diet-induced steatohepatitis were investigated in obese, diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats. Components of the renin-angiotensin system were up-regulated in the livers of OLETF rats, compared with LETO rats. In OLETF, but not LETO, rats, oral administration of olmesartan for 8 weeks ameliorated insulin resistance. Moreover, olmesartan suppressed MCD diet-induced hepatic steatosis and the hepatic expression of lipogenic genes (sterol regulatory element-binding protein-1c and fatty acid synthase) in OLETF, but not LETO, rats. In both OLETF and LETO rats, olmesartan inhibited hepatic oxidative stress (4-hydroxy-2-nonenal-modified protein) and expression of NADPH oxidase. Olmesartan also inhibited hepatic fibrosis, stellate cell activation, and expression of fibrogenic genes (transforming growth factor-beta, alpha 1 [I] procollagen, plasminogen activator inhibitor-1) in both OLETF and LETO rats. In conclusion, pharmacological blockade of the angiotensin II type 1 receptor slows the development of steatohepatitis in the OLETF rat model. This angiotensin II type 1 receptor blocker may exert insulin resistance-associated effects against hepatic steatosis and inflammation as well as direct effects against the generation of reactive oxygen species and fibrogenesis.
Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Choline Deficiency; Disease Models, Animal; Fatty Acids; Fatty Liver; Imidazoles; Insulin Resistance; Liver Cirrhosis, Experimental; Male; Methionine; Oxidative Stress; RNA, Messenger; Rats; Rats, Long-Evans; Sterol Regulatory Element Binding Protein 1; Tetrazoles; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha
PubMed: 18501344
DOI: 10.1016/j.ejphar.2008.04.028 -
Integrated Blood Pressure Control 2010Hypertension is a major health problem worldwide and remains underdiagnosed and undertreated. Although public awareness and control of hypertension have improved over...
Hypertension is a major health problem worldwide and remains underdiagnosed and undertreated. Although public awareness and control of hypertension have improved over the last decade, only one-third of hypertensive patients achieve the rather conservative blood pressure (BP) goal of <140/90 mmHg. Most hypertensive patients require more than one drug for optimum BP control. Expert panels recommend use of combination therapy with two or more medications for Stage 2 and higher hypertension and in high-risk patients. However, the use of multiple drugs reduces patient compliance. Fixed-dose combination therapy helps improve patient compliance and thus achieve the target BP. Dose titration of the individual constituent drugs is recommended before switching to an equivalent fixed-dose combination. Randomized, controlled trials have shown that the fixed-dose combination of amlodipine-olmesartan medoxomil is more effective in lowering BP than monotherapy with either of these agents, with a similar side effect profile.
PubMed: 21949631
DOI: 10.2147/IBPC.S6662 -
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