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Identification
NameOlmesartan
Accession NumberDB00275  (APRD00223)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Olmesartan is an antihypertensive agent, which belongs to the class of medications called angiotensin II receptor blockers. It is indicated for the treatment of high blood pressure and is marketed under the name Olmetec®. The FDA label includes a black-box warning of injury and death to the fetus, so women of child-bearing age need to be warned and take the necessary precautions. Olmesartan is also contraindicated in diabetes mellitus patients taking aliskiren.

Structure
Thumb
Synonyms
4-(1-hydroxy-1-methylethyl)-2-propyl-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylic acid
4-(hydroxy-1-methylethyl)-2-propyl-1-{[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylic acid
External Identifiers
  • DE-092
  • RNH-6270
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Benicartablet, film coated40 mg/1oralDaiichi Sankyo, Inc.2002-04-25Not applicableUs
Benicartablet, film coated20 mg/1oralCardinal Health2002-04-25Not applicableUs
Benicartablet, film coated40 mg/1oralLake Erie Medical & Surgical Supply DBA Quality Care Products LLC2012-02-22Not applicableUs
Benicartablet, film coated5 mg/1oralCarilion Materials Management2002-04-25Not applicableUs
Benicartablet, film coated20 mg/1oralDaiichi Sankyo, Inc.2002-04-25Not applicableUs
Benicartablet, film coated20 mg/1oralPhysicians Total Care, Inc.2004-01-30Not applicableUs
Benicartablet, film coated5 mg/1oralDaiichi Sankyo, Inc.2002-04-25Not applicableUs
Benicartablet, film coated40 mg/1oralPhysicians Total Care, Inc.2003-08-06Not applicableUs
Benicartablet, film coated20 mg/1oralbryant ranch prepack2002-04-25Not applicableUs
Benicartablet, film coated20 mg/1oralREMEDYREPACK INC.2013-10-042016-04-05Us
Benicartablet, film coated40 mg/1oralbryant ranch prepack2002-04-25Not applicableUs
Benicartablet, film coated40 mg/1oralMed Health Pharma, LLC2012-02-02Not applicableUs
Benicartablet, film coated40 mg/1oralPd Rx Pharmaceuticals, Inc.2002-04-25Not applicableUs
Benicartablet, film coated20 mg/1oralMed Health Pharma, LLC2012-02-02Not applicableUs
Benicartablet, film coated20 mg/1oralCardinal Health2002-04-25Not applicableUs
Benicartablet, film coated5 mg/1oralMed Health Pharma, LLC2012-02-02Not applicableUs
Benicartablet, film coated40 mg/1oralCardinal Health2002-04-25Not applicableUs
Benicartablet, film coated20 mg/1oralLake Erie Medical & Surgical Supply DBA Quality Care Products LLC2012-02-22Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ErastapexNot Available
GolmeNot Available
OlmetecNot Available
WinBPNot Available
Brand mixtures
NameLabellerIngredients
AzorPhysicians Total Care, Inc.
Benicar HctLake Erie Medical & Surgical Supply DBA Quality Care Products LLC
TribenzorDaiichi Sankyo, Inc.
Salts
Name/CASStructureProperties
Olmesartan medoxomil
144689-63-4
Thumb
  • InChI Key: UQGKUQLKSCSZGY-UHFFFAOYSA-N
  • Monoisotopic Mass: 558.22268271
  • Average Mass: 558.595
DBSALT001815
Categories
UNII8W1IQP3U10
CAS number144689-24-7
WeightAverage: 446.5016
Monoisotopic: 446.206638728
Chemical FormulaC24H26N6O3
InChI KeyInChIKey=VTRAEEWXHOVJFV-UHFFFAOYSA-N
InChI
InChI=1S/C24H26N6O3/c1-4-7-19-25-21(24(2,3)33)20(23(31)32)30(19)14-15-10-12-16(13-11-15)17-8-5-6-9-18(17)22-26-28-29-27-22/h5-6,8-13,33H,4,7,14H2,1-3H3,(H,31,32)(H,26,27,28,29)
IUPAC Name
4-(2-hydroxypropan-2-yl)-2-propyl-1-({4-[2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-imidazole-5-carboxylic acid
SMILES
CCCC1=NC(=C(N1CC1=CC=C(C=C1)C1=C(C=CC=C1)C1=NN=NN1)C(O)=O)C(C)(C)O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as biphenyltetrazoles and derivatives. These are organic compounds containing a biphenyl attached to a tetrazole. A carbon atom of the biphenyl moiety is boned to a carbon or the nitrogen atom of the tetrazole moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzoles
Sub ClassTetrazoles
Direct ParentBiphenyltetrazoles and derivatives
Alternative Parents
Substituents
  • Biphenyltetrazole
  • Biphenyl
  • 1,2,4,5-tetrasubstituted imidazole
  • Phenylmethylamine
  • Benzenoid
  • N-substituted imidazole
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Tertiary alcohol
  • Imidazole
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Aromatic alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of hypertension.
PharmacodynamicsOlmesartan is a specific angiotensin II type 1 (AT1) receptor antagonist, which blocks the blood pressure increasing effects of angiotensin II via the renin-angiotensin-aldosterone system (RAAS). During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from granular cells of the juxtaglomerular apparatus in the kidneys. Renin cleaves circulating angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing total peripheral resistance, increasing sodium and water reabsorption in the kidneys via aldosterone secretion, and altering cardiovascular structure. Angiotensin II binds to two receptors: AT1 and AT2. AT1 is a G-protein coupled receptor (GPCR) that mediates the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Angiotensin receptor blockers (ARBs) are non-peptide competitive inhibitors of AT1. ARBs block the ability of angiotensin II to stimulate pressor and cell proliferative effects. Unlike ACE inhibitors, ARBs do not affect bradykinin-induced vasodilation. The overall effect of ARBs is a decrease in blood pressure.
Mechanism of actionOlmesartan is an ARB that selectively inhibits the binding of angiotensin II to AT1, which is found in many tissues such as vascular smooth muscle and the adrenal glands. This effectively inhibits the AT1-mediated vasoconstrictive and aldosterone-secreting effects of angiotensin II and results in a decrease in vascular resistance and blood pressure. Olmesartan is selective for AT1 and has a 12,500 times greater affinity for AT1 than the AT2 receptor. Also unlike the well-known ARB losartan, olmesartan does not have an active metabolite or possess uricosuric effects.
Related Articles
AbsorptionBioavailability is about 26%. Food does not affect the bioavailability of olmesartan.
Volume of distribution

The volume of distribution is 17 L and olmesartan poorly crosses the blood brain barrier.

Protein bindingHighly bound to plasma proteins (99%) and does not penetrate red blood cells.
Metabolism

Olmesartan is rapidly and completely bioactivated by ester hydrolysis to olmesartan during absorption from the gastrointestinal tract. There is virtually no further metabolism of olmesartan.

Route of eliminationOlmesartan is elminated unchanged in the urine (35% to 50%) and the remainder in the feces.
Half lifeThe half life is approximately 13 hours.
Clearance
  • Total plasma cl=1.3 L/h
  • Renal cl=0.6 L/h
ToxicityThe main symptoms of overdose include low blood pressure and fast heartbeat.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Olmesartan Action PathwayDrug actionSMP00163
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier-0.8719
Caco-2 permeable-0.6865
P-glycoprotein substrateSubstrate0.7247
P-glycoprotein inhibitor INon-inhibitor0.5917
P-glycoprotein inhibitor IIInhibitor0.6029
Renal organic cation transporterNon-inhibitor0.807
CYP450 2C9 substrateNon-substrate0.7429
CYP450 2D6 substrateNon-substrate0.8602
CYP450 3A4 substrateNon-substrate0.5149
CYP450 1A2 substrateNon-inhibitor0.782
CYP450 2C9 inhibitorInhibitor0.5816
CYP450 2D6 inhibitorNon-inhibitor0.8059
CYP450 2C19 inhibitorInhibitor0.6604
CYP450 3A4 inhibitorInhibitor0.7409
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8396
Ames testNon AMES toxic0.6203
CarcinogenicityNon-carcinogens0.6871
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6599 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9254
hERG inhibition (predictor II)Non-inhibitor0.6427
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Daiichi sankyo inc
  • Daiichi Sankyo
Packagers
Dosage forms
FormRouteStrength
Tablet, film coatedoral20 mg/1
Tablet, film coatedoral40 mg/1
Tablet, film coatedoral5 mg/1
Tablet, film coatedoral
Prices
Unit descriptionCostUnit
Benicar 5 mg tablet12.81USD tablet
Benicar hct 40-25 mg tablet4.93USD tablet
Benicar hct 40-12.5 mg tablet4.67USD tablet
Benicar hct 20-12.5 mg tablet3.94USD tablet
Benicar 40 mg tablet3.74USD tablet
Benicar 20 mg tablet2.97USD tablet
Olmetec 20 mg Tablet1.04USD tablet
Olmetec 40 mg Tablet1.04USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2061607 No1999-01-192012-02-20Canada
US5616599 Yes1996-10-252016-10-25Us
US6878703 Yes2002-05-192022-05-19Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point175-180 °CNot Available
logP5.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0105 mg/mLALOGPS
logP2.98ALOGPS
logP2.14ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)0.91ChemAxon
pKa (Strongest Basic)5.57ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area129.81 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity137.32 m3·mol-1ChemAxon
Polarizability47.46 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Lilach Hedvati, Gideon Pilarsky, “Preparation of olmesartan medoxomil.” U.S. Patent US20060069141, issued March 30, 2006.

US20060069141
General ReferencesNot Available
External Links
ATC CodesC09CA08C09DA08C09DB02C09DX03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (179 KB)
MSDSDownload (58.6 KB)
Interactions
Drug Interactions
Drug
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Olmesartan.
AlfuzosinAlfuzosin may increase the hypotensive activities of Olmesartan.
AliskirenAliskiren may increase the hyperkalemic activities of Olmesartan.
AmifostineOlmesartan may increase the hypotensive activities of Amifostine.
ArdeparinArdeparin may increase the hyperkalemic activities of Olmesartan.
BrimonidineBrimonidine may increase the antihypertensive activities of Olmesartan.
ButabarbitalButabarbital may increase the hypotensive activities of Olmesartan.
ButethalButethal may increase the hypotensive activities of Olmesartan.
CanagliflozinCanagliflozin may increase the hyperkalemic activities of Olmesartan.
CiprofloxacinOlmesartan may increase the arrhythmogenic activities of Ciprofloxacin.
ColesevelamThe serum concentration of Olmesartan can be decreased when it is combined with Colesevelam.
CyclosporineOlmesartan may increase the hyperkalemic activities of Cyclosporine.
DapoxetineDapoxetine may increase the orthostatic hypotensive activities of Olmesartan.
DiazoxideDiazoxide may increase the hypotensive activities of Olmesartan.
DrospirenoneOlmesartan may increase the hyperkalemic activities of Drospirenone.
DuloxetineOlmesartan may increase the orthostatic hypotensive activities of Duloxetine.
EltrombopagThe serum concentration of Olmesartan can be increased when it is combined with Eltrombopag.
EplerenoneEplerenone may increase the hyperkalemic activities of Olmesartan.
HeparinHeparin may increase the hyperkalemic activities of Olmesartan.
HeptabarbitalHeptabarbital may increase the hypotensive activities of Olmesartan.
HexobarbitalHexobarbital may increase the hypotensive activities of Olmesartan.
InfliximabThe risk or severity of adverse effects can be increased when Olmesartan is combined with Infliximab.
LevodopaOlmesartan may increase the orthostatic hypotensive activities of Levodopa.
LithiumThe serum concentration of Lithium can be increased when it is combined with Olmesartan.
MethohexitalMethohexital may increase the hypotensive activities of Olmesartan.
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Olmesartan.
MolsidomineMolsidomine may increase the hypotensive activities of Olmesartan.
MoxonidineMoxonidine may increase the hypotensive activities of Olmesartan.
NicorandilNicorandil may increase the hypotensive activities of Olmesartan.
ObinutuzumabOlmesartan may increase the hypotensive activities of Obinutuzumab.
PentobarbitalPentobarbital may increase the hypotensive activities of Olmesartan.
PentoxifyllinePentoxifylline may increase the hypotensive activities of Olmesartan.
PerindoprilThe risk or severity of adverse effects can be increased when Olmesartan is combined with Perindopril.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Olmesartan.
PrimidonePrimidone may increase the hypotensive activities of Olmesartan.
QuinineQuinine may increase the hypotensive activities of Olmesartan.
RisperidoneOlmesartan may increase the hypotensive activities of Risperidone.
RituximabOlmesartan may increase the hypotensive activities of Rituximab.
SecobarbitalSecobarbital may increase the hypotensive activities of Olmesartan.
TadalafilTadalafil may increase the antihypertensive activities of Olmesartan.
TeriflunomideThe serum concentration of Olmesartan can be increased when it is combined with Teriflunomide.
TolvaptanTolvaptan may increase the hyperkalemic activities of Olmesartan.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Olmesartan.
TreprostinilTreprostinil may increase the hypotensive activities of Olmesartan.
TriamtereneOlmesartan may increase the hyperkalemic activities of Triamterene.
TrimethoprimTrimethoprim may increase the hyperkalemic activities of Olmesartan.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Olmesartan.
VardenafilVardenafil may increase the antihypertensive activities of Olmesartan.
YohimbineYohimbine may decrease the antihypertensive activities of Olmesartan.
Food Interactions
  • Food does not affect the bioavailability of olmesartan.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Protein heterodimerization activity
Specific Function:
Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Gene Name:
AGTR1
Uniprot ID:
P30556
Molecular Weight:
41060.53 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Koike H, Sada T, Mizuno M: In vitro and in vivo pharmacology of olmesartan medoxomil, an angiotensin II type AT1 receptor antagonist. J Hypertens Suppl. 2001 Jun;19(1):S3-14. [PubMed:11451212 ]
  3. Ochiai K, Hu Q, Lee J, Mansoor A, Liu J, Wang X, Gong G, Murakami Y, Ishibashi Y, Shimada T, Zhang J: Functional and bioenergetic consequences of AT1 antagonist olmesartan medoxomil in hearts with postinfarction LV remodeling. J Cardiovasc Pharmacol. 2006 May;47(5):686-94. [PubMed:16775509 ]
  4. Warner GT, Jarvis B: Olmesartan medoxomil. Drugs. 2002;62(9):1345-53; discussion 1354-6. [PubMed:12076183 ]
  5. Mire DE, Silfani TN, Pugsley MK: A review of the structural and functional features of olmesartan medoxomil, an angiotensin receptor blocker. J Cardiovasc Pharmacol. 2005 Nov;46(5):585-93. [PubMed:16220064 ]
  6. Kreutz R, Bolbrinker J, Huber M: Pharmacokinetics of olmesartan medoxomil plus hydrochlorothiazide combination in healthy subjects. Clin Drug Investig. 2006;26(1):29-34. [PubMed:17163232 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinducer
General Function:
Organic anion transmembrane transporter activity
Specific Function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular Weight:
174205.64 Da
References
  1. Weiss J, Sauer A, Divac N, Herzog M, Schwedhelm E, Boger RH, Haefeli WE, Benndorf RA: Interaction of angiotensin receptor type 1 blockers with ATP-binding cassette transporters. Biopharm Drug Dispos. 2010 Mar;31(2-3):150-61. doi: 10.1002/bdd.699. [PubMed:20222053 ]
  2. Nakagomi-Hagihara R, Nakai D, Kawai K, Yoshigae Y, Tokui T, Abe T, Ikeda T: OATP1B1, OATP1B3, and mrp2 are involved in hepatobiliary transport of olmesartan, a novel angiotensin II blocker. Drug Metab Dispos. 2006 May;34(5):862-9. Epub 2006 Feb 24. [PubMed:16501004 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Molecular Weight:
77402.175 Da
References
  1. Nakagomi-Hagihara R, Nakai D, Kawai K, Yoshigae Y, Tokui T, Abe T, Ikeda T: OATP1B1, OATP1B3, and mrp2 are involved in hepatobiliary transport of olmesartan, a novel angiotensin II blocker. Drug Metab Dispos. 2006 May;34(5):862-9. Epub 2006 Feb 24. [PubMed:16501004 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
References
  1. Nakagomi-Hagihara R, Nakai D, Kawai K, Yoshigae Y, Tokui T, Abe T, Ikeda T: OATP1B1, OATP1B3, and mrp2 are involved in hepatobiliary transport of olmesartan, a novel angiotensin II blocker. Drug Metab Dispos. 2006 May;34(5):862-9. Epub 2006 Feb 24. [PubMed:16501004 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on May 30, 2016 03:19