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Identification
Name Eprosartan
Accession Number DB00876 (APRD00950)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Teveten
Brand name mixtures
  • Teveten Plus (Eprosartan Mesylate + Hydrochlorothiazide)
Categories
  • Antihypertensive Agents
  • Angiotensin II Type 1 Receptor Blockers
CAS number 133040-01-4
Weight Average: 424.513
Monoisotopic: 424.145677956
Chemical Formula C23H24N2O4S
InChI Key InChIKey=OROAFUQRIXKEMV-UHFFFAOYSA-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)
Plain Text
IUPAC Name
4-({2-butyl-5-[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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzyl Alcohols and Derivatives
  • Benzoates
  • Benzoyl Derivatives
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Benzoates
  • Carboxylic Acids and Derivatives
  • Benzene and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Imines
  • Benzoyl Derivatives
  • Cyanamides
  • Thiophenes
  • Dicarboxylic Acids
Pharmacology
Indication For 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).
Pharmacodynamics Angiotensin 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 action Eprosartan 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).
Absorption Absolute bioavailability following a single 300 mg oral dose of eprosartan is approximately 13%. Administering eprosartan with food delays absorption.
Volume of distribution Not Available
Protein binding Plasma 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 elimination Not Available
Half life The terminal elimination half-life of eprosartan following oral administration is typically 5 to 9 hours.
Clearance Not Available
Toxicity There 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 Not Available
Pharmacoeconomics
Manufacturers
  • Abbott laboratories
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Teveten hct 600-12.5 mg tablet 3.52 USD tablet
Teveten hct 600-25 mg tablet 3.42 USD tablet
Teveten 600 mg tablet 3.19 USD tablet
Teveten 400 mg tablet 2.83 USD tablet
Teveten 400 mg tiltab 1.24 USD tablet
Teveten 600 mg Tablet 1.18 USD tablet
Teveten 400 mg Tablet 0.79 USD tablet
Patents
Country Patent Number Approved Expires
United States 5656650 1994-08-12 2014-08-12
United States 5185351 1993-02-09 2010-02-09
Canada 2250395 2005-09-06 2017-03-26
Canada 2115170 2004-05-25 2012-08-12
Properties
State solid
Melting point 248-250oC (mesylate form)
Experimental Properties
Property Value Source
water solubility Insoluble (mesylate form) PhysProp
logP 3.9 PhysProp
Predicted Properties
Property Value Source
water solubility 8.66e-03 g/l ALOGPS
logP 3.57 ALOGPS
logP 2.91 ChemAxon Molconvert
logS -4.69 ALOGPS
pKa 4.38 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 92.42 ChemAxon Molconvert
rotatable bond count 10 ChemAxon Molconvert
refractivity 117.02 ChemAxon Molconvert
polarizability 45.06 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  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
  2. Hedner T: The clinical profile of the angiotensin II receptor blocker eprosartan. J Hypertens Suppl. 2002 Jun;20(5):S33-8. Pubmed
  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
  4. Ruilope L, Jager B: Eprosartan for the treatment of hypertension. Expert Opin Pharmacother. 2003 Jan;4(1):107-14. Pubmed
  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. Pubmed
  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
External Links
Resource Link
KEGG Drug D04040 Link_out
KEGG Compound C07467 Link_out
PubChem Compound 6398765 Link_out
PubChem Substance 46506765 Link_out
ChemSpider 54861 Link_out
ChEBI 4814 Link_out
ChEMBL 4814 Link_out
Therapeutic Targets Database DAP001367 Link_out
PharmGKB PA449481 Link_out
Drug Product Database 2243942 Link_out
RxList http://www.rxlist.com/cgi/generic3/eprosartan.htm Link_out
Drugs.com http://www.drugs.com/cdi/eprosartan.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/tev1538.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Eprosartan Link_out
ATC Codes
  • C09CA02
AHFS Codes
  • 24:32.08
PDB Entries Not Available
FDA label show (1.1 MB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
Targets

1. Type-1 angiotensin II receptor

Pharmacological action: yes
Actions: antagonist

Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P30556 Link_out
Gene: AGTR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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
  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
  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
  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
  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
  7. Hedner T: The clinical profile of the angiotensin II receptor blocker eprosartan. J Hypertens Suppl. 2002 Jun;20(5):S33-8. Pubmed
  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
  9. Ruilope L, Jager B: Eprosartan for the treatment of hypertension. Expert Opin Pharmacother. 2003 Jan;4(1):107-14. Pubmed
  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. Pubmed
  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
Enzymes

1. Cytochrome P450 2C9

Actions: inhibitor

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, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Transporters

1. Canalicular multispecific organic anion transporter 1

Actions: inducer

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:07

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.