Identification

Name
Ardeparin
Accession Number
DB00407  (APRD00803)
Type
Small Molecule
Groups
Approved, Investigational, Withdrawn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 Normiflo was withdrawn from the US market in March 2000.

Synonyms
Not Available
International/Other Brands
Normiflo (Wyeth-Ayerst (United States))
Categories
UNII
VL0L558GCB
CAS number
9005-49-6
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

For prevention of deep vein thrombosis, which may result in pulmonary embolism, following knee surgery.

Pharmacodynamics

Ardeparin, 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 action

Ardeparin 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.

TargetActionsOrganism
AAntithrombin-III
potentiator
Human
AHeparin cofactor 2
agonist
Human
Absorption

Well absorbed following subcutaneous administration, with a mean bioavailability of 92% (based on anti-factor Xa activity).

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

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

Route of elimination
Not Available
Half life

Elimination 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.

Clearance
Not Available
Toxicity

Symptoms of overdose may include excessive bleeding and bruising.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Ardeparin Action PathwayDrug action
Enoxaparin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1,2,6,7-3H)TestosteroneThe therapeutic efficacy of Ardeparin can be increased when used in combination with (1,2,6,7-3H)Testosterone.
(R)-warfarinThe risk or severity of bleeding can be increased when Ardeparin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Ardeparin is combined with (S)-Warfarin.
1-TestosteroneThe therapeutic efficacy of Ardeparin can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Ardeparin can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Ardeparin is combined with 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Ardeparin can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Ardeparin can be increased when used in combination with 5beta-dihydrotestosterone.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Ardeparin.
AcebutololThe risk or severity of hyperkalemia can be increased when Ardeparin is combined with Acebutolol.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D02980
PubChem Substance
46505194
Therapeutic Targets Database
DAP000428
PharmGKB
PA164754878
Drugs.com
Drugs.com Drug Page
Wikipedia
Ardeparin
MSDS
Download (65.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceAltered Heparin Response / Cardiopulmonary Bypass1
2CompletedPreventionVenous Thromboembolism (VTE)1
2TerminatedPreventionThrombosis Prophylaxis (Risk of Thrombosis Due to Central Venous Line (CVL)1
2WithdrawnTreatmentDiabetes, Diabetes Mellitus Type 11
3CompletedPreventionMalignancies / Venous Thromboembolism (VTE)1
3CompletedPreventionVenous Thromboembolism (VTE)5
3CompletedTreatmentDeep Vein Thrombosis (DVT)1
3RecruitingPreventionCatheter-Related Infections / Chronic Renal Failure (CRF)1
3TerminatedPreventionVenous Thromboembolism (VTE)1
4RecruitingTreatmentInfertilities1
Not AvailableRecruitingNot AvailableIntra Operative Bleeding, Blood Salvage1

Pharmacoeconomics

Manufacturers
  • Wyeth ayerst laboratories
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySolubleNot Available
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors IXa, Xa and XIa. Its inhibitory a...
Gene Name
SERPINC1
Uniprot ID
P01008
Uniprot Name
Antithrombin-III
Molecular Weight
52601.935 Da
References
  1. Mousa SA: The low molecular weight heparin, tinzaparin, in thrombosis and beyond. Cardiovasc Drug Rev. 2002 Fall;20(3):199-216. [PubMed:12397367]
  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:11287128]
  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:7632944]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT...
Gene Name
SERPIND1
Uniprot ID
P05546
Uniprot Name
Heparin cofactor 2
Molecular Weight
57070.16 Da
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:17139284]
  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:17016423]
  3. Mousa SA: The low molecular weight heparin, tinzaparin, in thrombosis and beyond. Cardiovasc Drug Rev. 2002 Fall;20(3):199-216. [PubMed:12397367]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:43