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Identification
NameArdeparin
Accession NumberDB00407  (APRD00803)
Typesmall molecule
Groupsapproved, withdrawn
Description

Ardeparin, marketed under the US trade name Normiflo, is a low molecular weight heparin (LMWH) anticoagulant used for the prevention of postoperative venous thrombosis. Ardeparin is derived via peroxide degradation of heparin extracted from porcine intestinal mucosa. Its molecular weight ranges from 2000 to 15,000 with an average molecular weight of 5500 to 6500. Normiflo was withdrawn from the US market in March 2000.

Structure
Thumb
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
NormifloWyeth-Ayerst (United States)
Brand mixturesNot Available
CategoriesNot Available
CAS numberNot Available
WeightAverage: 1134.928
Monoisotopic: 1134.006993818
Chemical FormulaC26H42N2O37S5
InChI KeyInChIKey=HTTJABKRGRZYRN-UHFFFAOYSA-N
InChI
InChI=1S/C26H42N2O37S5/c1-4(30)27-7-9(31)13(6(56-23(7)39)3-55-67(43,44)45)58-26-19(65-70(52,53)54)12(34)16(20(62-26)22(37)38)60-24-8(28-66(40,41)42)15(63-68(46,47)48)14(5(2-29)57-24)59-25-18(64-69(49,50)51)11(33)10(32)17(61-25)21(35)36/h5-20,23-26,28-29,31-34,39H,2-3H2,1H3,(H,27,30)(H,35,36)(H,37,38)(H,40,41,42)(H,43,44,45)(H,46,47,48)(H,49,50,51)(H,52,53,54)
IUPAC Name
3-[(5-{[6-carboxy-4,5-dihydroxy-3-(sulfooxy)oxan-2-yl]oxy}-6-(hydroxymethyl)-3-(sulfoamino)-4-(sulfooxy)oxan-2-yl)oxy]-6-({5-acetamido-4,6-dihydroxy-2-[(sulfooxy)methyl]oxan-3-yl}oxy)-4-hydroxy-5-(sulfooxy)oxane-2-carboxylic acid
SMILES
CC(=O)NC1C(O)OC(COS(O)(=O)=O)C(OC2OC(C(OC3OC(CO)C(OC4OC(C(O)C(O)C4OS(O)(=O)=O)C(O)=O)C(OS(O)(=O)=O)C3NS(O)(=O)=O)C(O)C2OS(O)(=O)=O)C(O)=O)C1O
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 prevention of deep vein thrombosis, which may result in pulmonary embolism, following knee surgery.
PharmacodynamicsArdeparin, an anticoagulant, is a fractionated heparin. It acts at multiple sites in the normal coagulation system to inhibit reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo.
Mechanism of actionArdeparin binds to antithrombin III, accelerating its activity in inactivating factor Xa and thrombin, thereby inhibiting thrombosis. Ardeparin also binds to heparin cofactor II, inhibiting thrombin. Ardeparin does not effect prothrombin time (PT) assays and may prolong activated partial thromboplastin time (APTT). Ardeparin has double the anti-factor Xa activity versus anti-factor IIa activity, compared to unfractionated heparin which has approximately equal anti-factor Xa activity and anti-factor IIa activity.
AbsorptionWell absorbed following subcutaneous administration, with a mean bioavailability of 92% (based on anti-factor Xa activity).
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Liver and the reticulo-endothelial system are the sites of biotransformation.

Route of eliminationNot Available
Half lifeElimination half-life for anti-factor Xa activity averages 3.3 hours following a single intravenous dose, while elimination half-life for anti-factor IIa activity averages 1.2 hours following a single intravenous dose.
ClearanceNot Available
ToxicitySymptoms of overdose may include excessive bleeding and bruising.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Ardeparin Action PathwayDrug actionSMP00275
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption Not Available Not Available
Blood Brain Barrier Not Available Not Available
Caco-2 permeable Not Available Not Available
P-glycoprotein substrate Not Available Not Available
P-glycoprotein inhibitor I Not Available Not Available
P-glycoprotein inhibitor II Not Available Not Available
Renal organic cation transporter Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 1A2 substrate Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 2C19 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 inhibitory promiscuity Not Available Not Available
Ames test Not Available Not Available
Carcinogenicity Not Available Not Available
Biodegradation Not Available Not Available
Rat acute toxicity Not Available Not applicable
hERG inhibition (predictor I) Not Available Not Available
hERG inhibition (predictor II) Not Available Not Available
Pharmacoeconomics
Manufacturers
  • Wyeth ayerst laboratories
PackagersNot Available
Dosage forms
FormRouteStrength
InjectionSubcutaneous
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilitySolubleNot Available
Predicted Properties
PropertyValueSource
water solubility1.08e+01 g/lALOGPS
logP-1.7ALOGPS
logP-8.3ChemAxon
logS-2ALOGPS
pKa (strongest acidic)-2.8ChemAxon
physiological charge-7ChemAxon
hydrogen acceptor count33ChemAxon
hydrogen donor count15ChemAxon
polar surface area610.49ChemAxon
rotatable bond count20ChemAxon
refractivity195.91ChemAxon
polarizability93.37ChemAxon
number of rings4ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
PubChem Compound772
PubChem Substance46505194
ChemSpider751
Therapeutic Targets DatabaseDAP000428
PharmGKBPA164754878
Drugs.comhttp://www.drugs.com/mtm/ardeparin.html
WikipediaArdeparin
ATC CodesB01AB05B01AB01
AHFS Codes
  • 20:12.04.16
  • 92:00.00
PDB Entries
FDA labelNot Available
MSDSshow(65.5 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Antithrombin-III

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Antithrombin-III P01008 Details

References:

  1. Mousa SA: The low molecular weight heparin, tinzaparin, in thrombosis and beyond. Cardiovasc Drug Rev. 2002 Fall;20(3):199-216. Pubmed
  2. Lin P, Sinha U, Betz A: Antithrombin binding of low molecular weight heparins and inhibition of factor Xa. Biochim Biophys Acta. 2001 Apr 3;1526(1):105-13. Pubmed
  3. Shaughnessy SG, Young E, Deschamps P, Hirsh J: The effects of low molecular weight and standard heparin on calcium loss from fetal rat calvaria. Blood. 1995 Aug 15;86(4):1368-73. Pubmed

2. Heparin cofactor 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Heparin cofactor 2 P05546 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Mousa SA: The low molecular weight heparin, tinzaparin, in thrombosis and beyond. Cardiovasc Drug Rev. 2002 Fall;20(3):199-216. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:10