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Identification
NameEnoxaparin
Accession NumberDB01225  (APRD00068)
Typesmall molecule
Groupsapproved
Description

Enoxaparin is a low molecular weight heparin. Enoxaparin is used to prevent and treat deep vein thrombosis or pulmonary embolism, and is given as a subcutaneous injection. Enoxaparin binds to and accelerates the activity of antithrombin III. By activating antithrombin III, enoxaparin preferentially potentiates the inhibition of coagulation factors Xa and IIa. Factor Xa catalyzes the conversion of prothrombin to thrombin, so enoxaparin’s inhibition of this process results in decreased thrombin and ultimately the prevention of fibrin clot formation. Low molecular weight heparins are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.

Structure
Thumb
Synonyms
SynonymLanguageCode
LMWHNot AvailableNot Available
Low Molecular Weight HeparinNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ClexaneNot Available
LovenoxNot Available
Lovenox HPNot Available
Brand mixturesNot Available
Categories
CAS number9005-49-6
WeightNot Available
Chemical FormulaC26H42N2O37S5
InChI KeyHTTJABKRGRZYRN-UHFFFAOYSA-N
InChINot Available
IUPAC NameNot Available
SMILESNot Available
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganooxygen Compounds
ClassCarbohydrates and Carbohydrate Conjugates
SubclassTetrasaccharides
Direct parentTetrahexoses
Alternative parentsN-acyl-alpha-hexosamines; O-Glucuronides; O-glycosyl Compounds; Pyran Carboxylic Acids; Beta Hydroxy Acids and Derivatives; Sulfuric Acid Monoesters; Oxanes; Dicarboxylic Acids and Derivatives; Secondary Carboxylic Acid Amides; Secondary Alcohols; Hemiacetals; 1,2-Diols; Polyamines; Carboxylic Acids; Primary Alcohols; Acetals; Enolates
Substituentsn-acyl-alpha-hexosamine; 1-o-glucuronide; o-glucuronide; glucuronic acid or derivative; glycosyl compound; o-glycosyl compound; glucosamine; amino sugar; pyran carboxylic acid; pyran carboxylic acid or derivative; sulfuric acid monoester; beta-hydroxy acid; dicarboxylic acid derivative; oxane; sulfate-ester; hydroxy acid; sulfuric acid derivative; secondary alcohol; secondary carboxylic acid amide; 1,2-diol; hemiacetal; carboxamide group; polyol; ether; acetal; polyamine; enolate; carboxylic acid; primary alcohol; carboxylic acid derivative; alcohol; organonitrogen compound; amine
Classification descriptionThis compound belongs to the tetrahexoses. These are tetrasaccharides containing four hexose carbohydrates.
Pharmacology
IndicationFor the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism, and also for the prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin.
PharmacodynamicsEnoxaparin is a highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from 3800 to 5000 daltons. Enoxaparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Enoxaparin is a well known and commonly used anticoagulant which has antithrombotic properties. Enoxaparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Enoxaparin acts at multiple sites in the normal coagulation system. Small amounts of enoxaparin in combination with antithrombin III (enoxaparin cofactor) can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin. Once active thrombosis has developed, larger amounts of enoxaparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Enoxaparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor. Its use should be avoided in patients with a creatinine clearance less than 20mL/min. In these patients, unfractionated heparin should only be used. As for monitoring, active partial thromboplastin time (aPTT) will only increase at high doses of low molecular weight heparins (LMWH). Therefore, monitoring aPTT is not recommended. However, anti-Xa activity can be measured to monitor the efficacy of the LMWH.
Mechanism of actionThe mechanism of action of enoxaparin is antithrombin-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of enoxaparin is well correlated to the inhibition of factor Xa. Enoxaparin interacts with Antithrombin III, Prothrombin and Factor X. Enoxaparin binds to and accelerates the activity of antithrombin III. By activating antithrombin III, enoxaparin preferentially potentiates the inhibition of coagulation factors Xa and IIa.
AbsorptionMean absolute bioavailability of enoxaparin, after 1.5 mg/kg given subcutaneously, based on anti-Factor Xa activity is approximately 100% in healthy volunteers.
Volume of distribution
  • 4.3 L
Protein binding80% bound-albumin
Metabolism

Undergoes desulfation and polymerization via the liver

Route of eliminationEnoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerization to lower molecular weight species with much reduced biological potency. Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion of active and non-active fragments 40% of the dose.
Half life4.5 hours
ClearanceNot Available
ToxicityMouse, median lethal dose greater than 5000 mg/kg. Another side effect is heparin induced thrombocytopenia (HIT syndrome). HIT is caused by an immunological reaction that makes platelets form clots within the blood vessels, thereby using up coagulation factors.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Enoxaparin Action PathwayDrug actionSMP00272
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.9215
Blood Brain Barrier - 0.8366
Caco-2 permeable - 0.6496
P-glycoprotein substrate Non-substrate 0.698
P-glycoprotein inhibitor I Non-inhibitor 0.5818
P-glycoprotein inhibitor II Non-inhibitor 0.9771
Renal organic cation transporter Non-inhibitor 0.9454
CYP450 2C9 substrate Non-substrate 0.6694
CYP450 2D6 substrate Non-substrate 0.8196
CYP450 3A4 substrate Non-substrate 0.5842
CYP450 1A2 substrate Non-inhibitor 0.8157
CYP450 2C9 substrate Non-inhibitor 0.771
CYP450 2D6 substrate Non-inhibitor 0.8869
CYP450 2C19 substrate Non-inhibitor 0.7655
CYP450 3A4 substrate Non-inhibitor 0.9194
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9232
Ames test Non AMES toxic 0.5957
Carcinogenicity Non-carcinogens 0.694
Biodegradation Not ready biodegradable 0.851
Rat acute toxicity 2.3846 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9589
hERG inhibition (predictor II) Non-inhibitor 0.7157
Pharmacoeconomics
Manufacturers
  • Sandoz inc
  • Sanofi aventis us llc
Packagers
Dosage forms
FormRouteStrength
LiquidIntravenous
LiquidIrrigation
SolutionIntraperitoneal
SolutionIntravenous
SolutionSubcutaneous
Prices
Unit descriptionCostUnit
Lovenox 300 mg/3ml Solution 3ml Vial281.47USDvial
Lovenox 150 mg/ml Solution 1ml Syringe140.94USDsyringe
Lovenox 100 mg/ml Solution 1ml Syringe93.93USDsyringe
Lovenox 80 mg/0.8ml Solution 0.8ml Syringe75.14USDsyringe
Lovenox 60 mg/0.6ml Solution 0.6ml Syringe56.36USDsyringe
Lovenox 40 mg/0.4ml Solution 0.4ml Syringe37.53USDsyringe
Lovenox Hp (0.8Ml/1Ml Syringe) 150 mg/ml Syringe34.63USDsyringe
Lovenox 30 mg/0.3ml Solution 0.3ml Syringe28.15USDsyringe
Lovenox (0.4 - 1 Ml Syringe) 100 mg/ml Syringe23.09USDsyringe
Lovenox 100 mg/ml23.09USDsyringe
Lovenox (0.3 Ml Syringe) 30 mg/syr Syringe6.97USDsyringe
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States53896181995-02-142012-02-14
Canada20454332002-07-302011-06-25
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubility> 200 mg/mLNot Available
logP-13.2Not Available
Predicted PropertiesNot Available
Spectra
SpectraNot Available
References
Synthesis Reference

Jorgen I. Nielsen, “Process of using light absorption to control enzymatic depolymerization of heparin to produce low molecular weight heparin.” U.S. Patent US5106734, issued May, 1981.

US5106734
General ReferenceNot Available
External Links
ResourceLink
Therapeutic Targets DatabaseDAP000616
PharmGKBPA449463
Drug Product Database2242692
RxListhttp://www.rxlist.com/cgi/generic3/lovenox.htm
Drugs.comhttp://www.drugs.com/cdi/enoxaparin.html
WikipediaEnoxaparin
ATC CodesNot Available
AHFS Codes
  • 20:12.04.16
  • 92:00.00
PDB EntriesNot Available
FDA labelshow(1.44 MB)
MSDSNot Available
Interactions
Drug Interactions
Drug
ApixabanDue to pharmacodynamic interaction, a 50-60% increase in anti-Factor Xa activity may be observed with concomitant therapy.
Drotrecogin alfaCombination should be used with caution after weighing advantages and disadvantages. Low molecular weight heparins such as enoxaparin may increase the adverse effects of drotrecogin. Monitor for bleeding if used concomitantly.
Ginkgo bilobaAdditive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
TreprostinilThe prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the anticoagulant, Exoxaparin. Monitor for increased bleeding during concomitant thearpy.
Food Interactions
  • Avoid danshen, dong quai, evening primrose oil, gingko, policosanol, willow bark

Targets

1. Antithrombin-III

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Antithrombin-III P01008 Details

References:

  1. Peng K, Wang C, Pang BS, Yang YH: [Effects of thrombolysis and anticoagulation on the functions of vascular endothelial cells and coagulation and fibrinolysis in patients with pulmonary thromboembolism] Zhonghua Jie He He Hu Xi Za Zhi. 2005 Sep;28(9):596-9. Pubmed
  2. Lee S, Gibson CM: Enoxaparin in acute coronary syndromes. Expert Rev Cardiovasc Ther. 2007 May;5(3):387-99. Pubmed
  3. Bisio A, Vecchietti D, Citterio L, Guerrini M, Raman R, Bertini S, Eisele G, Naggi A, Sasisekharan R, Torri G: Structural features of low-molecular-weight heparins affecting their affinity to antithrombin. Thromb Haemost. 2009 Nov;102(5):865-73. Pubmed

2. Coagulation factor X

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Coagulation factor X P00742 Details

References:

  1. Graff J, Picard-Willems B, Harder S: Monitoring effects of direct FXa-inhibitors with a new one-step prothrombinase-induced clotting time (PiCT) assay: comparative in vitro investigation with heparin, enoxaparin, fondaparinux and DX 9065a. Int J Clin Pharmacol Ther. 2007 Apr;45(4):237-43. Pubmed
  2. Berges A, Laporte S, Epinat M, Zufferey P, Alamartine E, Tranchand B, Decousus H, Mismetti P: Anti-factor Xa activity of enoxaparin administered at prophylactic dosage to patients over 75 years old. Br J Clin Pharmacol. 2007 Oct;64(4):428-38. Epub 2007 May 17. Pubmed
  3. Sanchez-Pena P, Hulot JS, Urien S, Ankri A, Collet JP, Choussat R, Lechat P, Montalescot G: Anti-factor Xa kinetics after intravenous enoxaparin in patients undergoing percutaneous coronary intervention: a population model analysis. Br J Clin Pharmacol. 2005 Oct;60(4):364-73. Pubmed
  4. Dalmora SL, Junior LB, Schmidt CA, Vaccari SF, Oliveira PR, Codevilla CF: Validation of the anti-factor Xa assay for the potency assessment of enoxaparin in pharmaceutical formulations. J AOAC Int. 2004 Nov-Dec;87(6):1305-8. Pubmed
  5. Paige JT, Gouda BP, Gaitor-Stampley V, Scalia PG, Klainer TE, Raum WJ, Martin LF: No correlation between anti-factor Xa levels, low-molecular-weight heparin, and bleeding after gastric bypass. Surg Obes Relat Dis. 2007 Jul-Aug;3(4):469-75. Epub 2007 Jun 12. Pubmed

Enzymes

1. Myeloperoxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: Other

Components

Name UniProt ID Details
Myeloperoxidase P05164 Details

References:

  1. Rudolph TK, Rudolph V, Witte A, Klinke A, Szoecs K, Lau D, Heitzer T, Meinertz T, Baldus S: Liberation of vessel adherent myeloperoxidase by enoxaparin improves endothelial function. Int J Cardiol. 2010 Apr 1;140(1):42-7. Epub 2008 Dec 2. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on June 05, 2014 12:17