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Identification
NameEprosartan
Accession NumberDB00876  (APRD00950)
TypeSmall Molecule
GroupsApproved
Description

Eprosartan is an angiotensin II receptor antagonist used for the treatment of high blood pressure. It acts on the renin-angiotensin system in two ways to decrease total peripheral resistance. First, it blocks the binding of angiotensin II to AT1 receptors in vascular smooth muscle, causing vascular dilatation. Second, it inhibits sympathetic norepinephrine production, further reducing blood pressure.

Structure
Thumb
Synonyms
(e)-2-Butyl-1-(P-carboxybenzyl)-alpha-2-thenylimidazole-5-acrylic acid
(e)-3-[2-N-Butyl-1-{(4-carboxyphenyl)methyl}-1H-imidazol-5-yl]-2-(2-thienyl)methyl-2-propenoic acid
(e)-Alpha{[2-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazole-5-yl]methylene}-2-thiopheneproprionic acid
Eprosartan
Éprosartan
Eprosartan
Eprosartanum
External Identifiers
  • SKF 108566
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tevetentablet400 mg/1oralAbb Vie Inc.2010-05-242016-04-05Us
Tevetentablet600 mgoralBgp Pharma Ulc2001-05-25Not applicableCanada
Tevetentablet400 mgoralBgp Pharma Ulc2000-09-08Not applicableCanada
Tevetentablet600 mg/1oralAbb Vie Inc.2010-05-242016-04-05Us
Teveten Tablets 300 mgtablet300 mgoralSolvay Pharma Inc2000-09-082003-01-02Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Eprosartan Mesylatetablet, film coated600 mg/1oralMylan Pharmaceuticals Inc.2011-12-20Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
EprozarINTAS Pharmaceuticals
FuturanMerck
Brand mixtures
NameLabellerIngredients
Teveten HctAbb Vie Inc.
Teveten PlusBgp Pharma Ulc
Salts
Name/CASStructureProperties
Eprosartan mesylate
ThumbNot applicableDBSALT000927
Categories
UNII2KH13Z0S0Y
CAS number133040-01-4
WeightAverage: 424.513
Monoisotopic: 424.145677956
Chemical FormulaC23H24N2O4S
InChI KeyInChIKey=OROAFUQRIXKEMV-LDADJPATSA-N
InChI
InChI=1S/C23H24N2O4S/c1-2-3-6-21-24-14-19(12-18(23(28)29)13-20-5-4-11-30-20)25(21)15-16-7-9-17(10-8-16)22(26)27/h4-5,7-12,14H,2-3,6,13,15H2,1H3,(H,26,27)(H,28,29)/b18-12+
IUPAC Name
4-({2-butyl-5-[(1E)-2-carboxy-2-(thiophen-2-ylmethyl)eth-1-en-1-yl]-1H-imidazol-1-yl}methyl)benzoic acid
SMILES
CCCCC1=NC=C(\C=C(/CC2=CC=CS2)C(O)=O)N1CC1=CC=C(C=C1)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzoic acids. These are organic Compounds containing a benzene ring which bears at least one carboxyl group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentBenzoic acids
Alternative Parents
Substituents
  • Benzoic acid
  • Trisubstituted imidazole
  • Phenylmethylamine
  • Imidazolyl carboxylic acid derivative
  • Benzoyl
  • 1,2,5-trisubstituted-imidazole
  • N-substituted imidazole
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Thiophene
  • Imidazole
  • Azole
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the management of hypertension alone or in combination with other classes of antihypertensive agents. Also used as a first-line agent in the treatment of diabetic nephropathy, as well as a second-line agent in the treatment of congestive heart failure (only in those intolerant of ACE inhibitors).
PharmacodynamicsAngiotensin II, the principal pressor agent of the renin-angiotensin system, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme [kininase II]. It is responsible for effects such as vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Eprosartan selectively blocks the binding of angiotensin II to the AT1 receptor, which in turn leads to multiple effects including vasodilation, a reduction in the secretion of vasopressin, and reduction in the production and secretion of aldosterone. The resulting effect is a decrease in blood pressure.
Mechanism of actionEprosartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues (e.g., vascular smooth muscle, adrenal gland). There is also an AT2 receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Eprosartan does not exhibit any partial agonist activity at the AT1 receptor. Its affinity for the AT1 receptor is 1,000 times greater than for the AT2 receptor. In vitro binding studies indicate that eprosartan is a reversible, competitive inhibitor of the AT1 receptor. Eprosartan has also been shown to bind to AT1 receptors both presynaptically and synaptically. Its action on presynaptic AT1 receptors results in the inhibition of sympathetically stimulated noradrenaline release. Unlike ACE inhibitors, eprosartan and other ARBs do not interfere with response to bradykinins and substance P, which allows for the absence of adverse effects that are present in ACE inhibitors (eg. dry cough).
Related Articles
AbsorptionAbsolute bioavailability following a single 300 mg oral dose of eprosartan is approximately 13%. Administering eprosartan with food delays absorption.
Volume of distributionNot Available
Protein bindingPlasma protein binding of eprosartan is high (approximately 98%) and constant over the concentration range achieved with therapeutic doses.
Metabolism

Eprosartan is not metabolized by the cytochrome P450 system. It is mainly eliminated as unchanged drug. Less than 2% of an oral dose is excreted in the urine as a glucuronide.

Route of eliminationNot Available
Half lifeThe terminal elimination half-life of eprosartan following oral administration is typically 5 to 9 hours.
ClearanceNot Available
ToxicityThere was no mortality in rats and mice receiving oral doses of up to 3000 mg eprosartan/kg and in dogs receiving oral doses of up to 1000 mg eprosartan/kg.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Eprosartan Action PathwayDrug actionSMP00159
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9863
Blood Brain Barrier-0.6931
Caco-2 permeable-0.6261
P-glycoprotein substrateSubstrate0.8011
P-glycoprotein inhibitor INon-inhibitor0.8577
P-glycoprotein inhibitor IINon-inhibitor0.9574
Renal organic cation transporterNon-inhibitor0.7673
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7557
CYP450 1A2 substrateNon-inhibitor0.5798
CYP450 2C9 inhibitorNon-inhibitor0.6617
CYP450 2D6 inhibitorNon-inhibitor0.8325
CYP450 2C19 inhibitorNon-inhibitor0.6234
CYP450 3A4 inhibitorNon-inhibitor0.6086
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.644
Ames testNon AMES toxic0.7313
CarcinogenicityNon-carcinogens0.9454
BiodegradationNot ready biodegradable0.6117
Rat acute toxicity2.4288 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9464
hERG inhibition (predictor II)Non-inhibitor0.8827
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Abbott laboratories
Packagers
Dosage forms
FormRouteStrength
Tablet, film coatedoral600 mg/1
Tabletoral400 mg
Tabletoral400 mg/1
Tabletoral600 mg
Tabletoral600 mg/1
Tabletoral
Tabletoral300 mg
Prices
Unit descriptionCostUnit
Teveten hct 600-12.5 mg tablet3.52USD tablet
Teveten hct 600-25 mg tablet3.42USD tablet
Teveten 600 mg tablet3.19USD tablet
Teveten 400 mg tablet2.83USD tablet
Teveten 400 mg tiltab1.24USD tablet
Teveten 600 mg Tablet1.18USD tablet
Teveten 400 mg Tablet0.79USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2115170 No2004-05-252012-08-12Canada
CA2250395 No2005-09-062017-03-26Canada
US5185351 No1993-02-092010-02-09Us
US5656650 No1994-08-122014-08-12Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point248-250 °C (mesylate form)Not Available
water solubilityInsoluble (mesylate form)Not Available
logP3.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00866 mg/mLALOGPS
logP3.57ALOGPS
logP3.8ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)3.63ChemAxon
pKa (Strongest Basic)6.93ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area92.42 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity117.02 m3·mol-1ChemAxon
Polarizability45.29 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Richard T. Matsuoka, Peng Liu, “Process for preparing eprosartan using regioselective protection of 2,4-disubstituted-imidazole intermediates.” U.S. Patent US6294675, issued June, 1992.

US6294675
General References
  1. Ruilope L, Jager B, Prichard B: Eprosartan versus enalapril in elderly patients with hypertension: a double-blind, randomized trial. Blood Press. 2001;10(4):223-9. [PubMed:11800061 ]
  2. Hedner T: The clinical profile of the angiotensin II receptor blocker eprosartan. J Hypertens Suppl. 2002 Jun;20(5):S33-8. [PubMed:12184062 ]
  3. Puig JG, Lopez MA, Bueso TS, Bernardino JI, Jimenez RT: Clinical profile of eprosartan. Cardiovasc Drugs Ther. 2002 Dec;16(6):543-9. [PubMed:12766389 ]
  4. Ruilope L, Jager B: Eprosartan for the treatment of hypertension. Expert Opin Pharmacother. 2003 Jan;4(1):107-14. [PubMed:12517247 ]
  5. de la Sierra A, Ram CV: Introduction: The pharmacological profile of eprosartan--implications for cerebrovascular and cardiovascular risk reduction. Curr Med Res Opin. 2007 Nov;23 Suppl 5:S1-3. doi: 10.1185/030079907X260692. [PubMed:18093407 ]
  6. Blankestijn PJ, Rupp H: Clinical profile of eprosartan: a different angiotensin II receptor blocker. Cardiovasc Hematol Agents Med Chem. 2008 Oct;6(4):253-7. [PubMed:18855637 ]
External Links
ATC CodesC09CA02C09DA02
AHFS Codes
  • 24:32.08
PDB EntriesNot Available
FDA labelDownload (1.09 MB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Eprosartan.
AlfuzosinAlfuzosin may increase the hypotensive activities of Eprosartan.
AliskirenAliskiren may increase the hyperkalemic activities of Eprosartan.
AmifostineEprosartan may increase the hypotensive activities of Amifostine.
ArdeparinArdeparin may increase the hyperkalemic activities of Eprosartan.
BrimonidineBrimonidine may increase the antihypertensive activities of Eprosartan.
ButabarbitalButabarbital may increase the hypotensive activities of Eprosartan.
ButethalButethal may increase the hypotensive activities of Eprosartan.
CanagliflozinCanagliflozin may increase the hyperkalemic activities of Eprosartan.
CiprofloxacinEprosartan may increase the arrhythmogenic activities of Ciprofloxacin.
CyclosporineEprosartan may increase the hyperkalemic activities of Cyclosporine.
DapoxetineDapoxetine may increase the orthostatic hypotensive activities of Eprosartan.
DiazoxideDiazoxide may increase the hypotensive activities of Eprosartan.
DrospirenoneEprosartan may increase the hyperkalemic activities of Drospirenone.
DuloxetineEprosartan may increase the orthostatic hypotensive activities of Duloxetine.
EplerenoneEplerenone may increase the hyperkalemic activities of Eprosartan.
HeparinHeparin may increase the hyperkalemic activities of Eprosartan.
HeptabarbitalHeptabarbital may increase the hypotensive activities of Eprosartan.
HexobarbitalHexobarbital may increase the hypotensive activities of Eprosartan.
InfliximabThe risk or severity of adverse effects can be increased when Eprosartan is combined with Infliximab.
LevodopaEprosartan may increase the orthostatic hypotensive activities of Levodopa.
LithiumThe serum concentration of Lithium can be increased when it is combined with Eprosartan.
MethohexitalMethohexital may increase the hypotensive activities of Eprosartan.
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Eprosartan.
MolsidomineMolsidomine may increase the hypotensive activities of Eprosartan.
MoxonidineMoxonidine may increase the hypotensive activities of Eprosartan.
NicorandilNicorandil may increase the hypotensive activities of Eprosartan.
ObinutuzumabEprosartan may increase the hypotensive activities of Obinutuzumab.
PentobarbitalPentobarbital may increase the hypotensive activities of Eprosartan.
PentoxifyllinePentoxifylline may increase the hypotensive activities of Eprosartan.
PerindoprilThe risk or severity of adverse effects can be increased when Eprosartan is combined with Perindopril.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Eprosartan.
PrimidonePrimidone may increase the hypotensive activities of Eprosartan.
QuinineQuinine may increase the hypotensive activities of Eprosartan.
RisperidoneEprosartan may increase the hypotensive activities of Risperidone.
RituximabEprosartan may increase the hypotensive activities of Rituximab.
SecobarbitalSecobarbital may increase the hypotensive activities of Eprosartan.
TadalafilTadalafil may increase the antihypertensive activities of Eprosartan.
TolvaptanTolvaptan may increase the hyperkalemic activities of Eprosartan.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Eprosartan.
TreprostinilTreprostinil may increase the hypotensive activities of Eprosartan.
TriamtereneEprosartan may increase the hyperkalemic activities of Triamterene.
TrimethoprimTrimethoprim may increase the hyperkalemic activities of Eprosartan.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Eprosartan.
VardenafilVardenafil may increase the antihypertensive activities of Eprosartan.
YohimbineYohimbine may decrease the antihypertensive activities of Eprosartan.
Food Interactions
  • Take without regard to meals.

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. Heusser K, Vitkovsky J, Schmieder RE, Schobel HP: AT1 antagonism by eprosartan lowers heart rate variability and baroreflex gain. Auton Neurosci. 2003 Aug 29;107(1):45-51. [PubMed:12927226 ]
  3. Gremmler B, Kunert M, Schleiting H, Ulbricht LJ: Improvement of cardiac output in patients with severe heart failure by use of ACE-inhibitors combined with the AT1-antagonist eprosartan. Eur J Heart Fail. 2000 Jun;2(2):183-7. [PubMed:10856732 ]
  4. Suzuki G, Mishima T, Tanhehco EJ, Sharov VG, Todor A, Rostogi S, Gupta RC, Chaudhry PA, Anagnostopoulos PV, Nass O, Goldstein S, Sabbah HN: Effects of the AT1-receptor antagonist eprosartan on the progression of left ventricular dysfunction in dogs with heart failure. Br J Pharmacol. 2003 Jan;138(2):301-9. [PubMed:12540520 ]
  5. Ilson BE, Martin DE, Boike SC, Jorkasky DK: The effects of eprosartan, an angiotensin II AT1 receptor antagonist, on uric acid excretion in patients with mild to moderate essential hypertension. J Clin Pharmacol. 1998 May;38(5):437-41. [PubMed:9602957 ]
  6. Nap A, Mathy MJ, Balt JC, Pfaffendorf M, van Zwieten PA: Pre- and postsynaptic inhibitory potencies of the angiotensin AT1 receptor antagonists eprosartan and candesartan. Eur J Pharmacol. 2003 May 23;469(1-3):117-24. [PubMed:12782193 ]
  7. Hedner T: The clinical profile of the angiotensin II receptor blocker eprosartan. J Hypertens Suppl. 2002 Jun;20(5):S33-8. [PubMed:12184062 ]
  8. Puig JG, Lopez MA, Bueso TS, Bernardino JI, Jimenez RT: Clinical profile of eprosartan. Cardiovasc Drugs Ther. 2002 Dec;16(6):543-9. [PubMed:12766389 ]
  9. Ruilope L, Jager B: Eprosartan for the treatment of hypertension. Expert Opin Pharmacother. 2003 Jan;4(1):107-14. [PubMed:12517247 ]
  10. de la Sierra A, Ram CV: Introduction: The pharmacological profile of eprosartan--implications for cerebrovascular and cardiovascular risk reduction. Curr Med Res Opin. 2007 Nov;23 Suppl 5:S1-3. doi: 10.1185/030079907X260692. [PubMed:18093407 ]
  11. Murdoch DR, McDonagh TA, Farmer R, Morton JJ, McMurray JJ, Dargie HJ: ADEPT: Addition of the AT1 receptor antagonist eprosartan to ACE inhibitor therapy in chronic heart failure trial: hemodynamic and neurohormonal effects. Am Heart J. 2001 May;141(5):800-7. [PubMed:11320369 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on October 18, 2013 10:44