Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C29H30N6O6 |
| Molecular Weight | 558.5851 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCC1=NC(=C(N1CC2=CC=C(C=C2)C3=CC=CC=C3C4=NN=NN4)C(=O)OCC5=C(C)OC(=O)O5)C(C)(C)O
InChI
InChIKey=UQGKUQLKSCSZGY-UHFFFAOYSA-N
InChI=1S/C29H30N6O6/c1-5-8-23-30-25(29(3,4)38)24(27(36)39-16-22-17(2)40-28(37)41-22)35(23)15-18-11-13-19(14-12-18)20-9-6-7-10-21(20)26-31-33-34-32-26/h6-7,9-14,38H,5,8,15-16H2,1-4H3,(H,31,32,33,34)
| Molecular Formula | C29H30N6O6 |
| Molecular Weight | 558.5851 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/18547134Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021286s023lbl.pdf
https://www.ncbi.nlm.nih.gov/pubmed/19033634
https://www.ncbi.nlm.nih.gov/pubmed/12076183
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18547134
Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021286s023lbl.pdf
https://www.ncbi.nlm.nih.gov/pubmed/19033634
https://www.ncbi.nlm.nih.gov/pubmed/12076183
Olmesartan medoxomil, a prodrug, is hydrolyzed to olmesartan during absorption from the gastrointestinal tract. Olmesartan is a selective AT1 subtype angiotensin II receptor antagonist. Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in vascular smooth muscle. Oral olmesartan medoxomil 10-40 mg once daily is recommended for the treatment of adult patients with hypertension, this dosage has consistently helped achieve a double-digit reduction both in systolic and diastolic blood pressure, a reduction which is maintained for one year. Extensive clinical evidence from several large well designed trials and the clinical practice setting has confirmed the antihypertensive efficacy and good tolerability profile of oral olmesartan medoxomil, as monotherapy in patients with hypertension. Olmesartan medoxomil has shown no clinically important pharmacokinetic interactions with digoxin, warfarin or antacid (aluminium magnesium hydroxide). Adverse events were infrequent in clinical studies of olmesartan medoxomil and were similar to those attributed to placebo.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25478368
Curator's Comment: Olmesartan in a dose dependent manner showed increase in antiepileptic activity toward chemically induced seizure model in mice. Human data not available.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL227 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17572702 |
0.091 nM [Kd] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | BENICAR Approved UseBenicar is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with Benicar. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. It may be used alone or in combination with other antihypertensive agents. Launch Date2002 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
479.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17060062/ |
20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
OLMESARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
894.409 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25067982/ |
20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
OLMESARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
2204 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11451211 |
8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered: |
OLMESARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2594.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17060062/ |
20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
OLMESARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
4927.619 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25067982/ |
20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
OLMESARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
5975 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11451211 |
8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered: |
OLMESARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.458 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25067982/ |
20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
OLMESARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
12.5 h |
unknown, oral |
OLMESARTAN plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
14.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11451211 |
8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered: |
OLMESARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1% |
unknown, oral |
OLMESARTAN plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: |
unhealthy, 65-75 years Health Status: unhealthy Age Group: 65-75 years Sex: M+F Sources: |
|
320 mg single, oral Highest studied dose Dose: 320 mg Route: oral Route: single Dose: 320 mg Sources: |
healthy Health Status: healthy Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 14.0 |
no | |||
| yes [Km 20 uM] | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Modulation of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis by olmesartan and omega-3. | 2014-01-25 |
|
| Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). | 2013-12 |
|
| Early treatment with olmesartan prevents juxtamedullary glomerular podocyte injury and the onset of microalbuminuria in type 2 diabetic rats. | 2012-05 |
|
| Efficacy of Sevikar® compared to the combination of perindopril plus amlodipine on central arterial blood pressure in patients with moderate-to-severe hypertension: Rationale and design of the SEVITENSION study. | 2011-09 |
|
| Protective effects of angiotensin II type-1 receptor blockade with olmesartan on spinal cord ischemia-reperfusion injury: an experimental study on rats. | 2010-08 |
|
| Culture period-dependent change of function and expression of ATP-binding cassette transporters in Caco-2 cells. | 2009-09 |
|
| Olmesartan ameliorates myocardial function independent of blood pressure control in patients with mild-to-moderate hypertension. | 2009-07 |
|
| Olmesartan improves left ventricular function in pressure-overload hypertrophied rat heart by blocking angiotensin II receptor with synergic effects of upregulation of angiotensin converting enzyme 2. | 2009-04 |
|
| Reduction of albuminuria by angiotensin receptor blocker beyond blood pressure lowering: evaluation in megsin/receptor for advanced glycation end products/inducible nitric oxide synthase triple transgenic diabetic nephropathy mouse model. | 2008-12 |
|
| Aldosterone induces interleukin-18 through endothelin-1, angiotensin II, Rho/Rho-kinase, and PPARs in cardiomyocytes. | 2008-09 |
|
| Inhibition of advanced glycation end products: an implicit goal in clinical medicine for the treatment of diabetic nephropathy? | 2008-04 |
|
| Comparison of effects of olmesartan and telmisartan on blood pressure and metabolic parameters in Japanese early-stage type-2 diabetics with hypertension. | 2008-01 |
|
| Improvement of stunned myocardium in dogs with olmesartan, an angiotensin II type 1 receptor antagonist, is independent of type 2 receptors. | 2008 |
|
| Effect of olmesartan on oxidative stress in hemodialysis patients. | 2007-05 |
|
| Inhibition of Fas-associated apoptosis in granulation tissue cells accompanies attenuation of postinfarction left ventricular remodeling by olmesartan. | 2007-05 |
|
| Role of AT1 receptor in isoproterenol-induced cardiac hypertrophy and oxidative stress in mice. | 2007-04 |
|
| Pravastatin enhances beneficial effects of olmesartan on vascular injury of salt-sensitive hypertensive rats, via pleiotropic effects. | 2007-03 |
|
| Hydrochlorothiazide added to valsartan is more effective than when added to olmesartan in reducing blood pressure in moderately hypertensive patients inadequately controlled by monotherapy. | 2006-12-05 |
|
| Adding hydrochlorothiazide to olmesartan dose dependently improves 24-h blood pressure and response rates in mild-to-moderate hypertension. | 2005-11 |
|
| The regressive effect of an angiotensin II receptor blocker on formed fatty streaks in monkeys fed a high-cholesterol diet. | 2005-10 |
|
| Mechanism of permeability-enhancing effect of EDTA and boric acid on the corneal penetration of 4-[1-hydroxy-1-methylethyl]-2-propyl-1-[4-[2-[tetrazole-5-yl]phenyl]phenyl] methylimidazole-5-carboxylic acid monohydrate (CS-088). | 2005-08-11 |
|
| Self-association properties of 4-[1-hydroxy-1-methylethyl]-2-propyl-1-[4-[2-[tetrazole-5-yl]phenyl]phenyl] methylimidazole-5-carboxylic acid monohydrate (CS-088), an antiglaucoma ophthalmic agent. | 2005-08-11 |
|
| Angiotensin II infusion increases hepatic triglyceride production via its type 2 receptor in rats. | 2005-08 |
|
| Enhanced intrarenal angiotensinogen contributes to early renal injury in spontaneously hypertensive rats. | 2005-07 |
|
| Renin-angiotensin system modulates oxidative stress-induced endothelial cell apoptosis in rats. | 2005-06 |
|
| Olmesartan improves endothelin-induced hypertension and oxidative stress in rats. | 2004-07 |
|
| Clinical and experimental aspects of olmesartan medoxomil, a new angiotensin II receptor antagonist. | 2004 |
|
| Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy. | 2004 |
|
| Effects of temocapril and olmesartan on myocardial sympathetic nervous activity and fatty acid metabolism in rats with chronic beta-adrenergic stimulation. | 2003-01 |
Patents
Sample Use Guides
BENICAR (olmesartan medoxomil) tablets dosage.Adult hypertension: Starting dose - 20 mg once daily (dose range 20 - 40 mg once daily).Pediatric hypertension (6 - 16 years): Starting dose for patients with body weight 20 to <35 kg - 10 mg once daily, if body weight >35 kg - 20 mg once daily (dose range 10 - 20 mg once daily and 20 - 40 mg once daily, respectively)
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23800993
Pre-treatment with 100 nM olmesartan abolished Ang II-induced apoptosis in cultured mouse podocytes
| Substance Class |
Chemical
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6M97XTV3HD
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C66930
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QC09CA08
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QC09DB02
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C09DB02
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C097933
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758924
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CHEMBL1200692
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (HPLC)
EP
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METABOLITE ACTIVE -> PRODRUG |
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
UNSPECIFIED
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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ACTIVE MOIETY |