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Identification
NameLepirudin
Accession NumberDB00001  (BIOD00024, BTD00024)
TypeBiotech
GroupsApproved
Description

Lepirudin is identical to natural hirudin except for substitution of leucine for isoleucine at the N-terminal end of the molecule and the absence of a sulfate group on the tyrosine at position 63. It is produced via yeast cells.

Protein structureDb00001
Protein chemical formulaC287H440N80O110S6
Protein average weight6963.4250
Sequences
>DB00001 sequence
LVYTDCTESGQNLCLCEGSNVCGQGNKCILGSDGEKNQCVTGEGTPKPQSHNDGDFEEIP
EEYLQ
Download FASTA Format
Synonyms
SynonymLanguageCode
Hirudin variant-1Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
RefludanBerlex Labs
Brand mixturesNot Available
Categories
CAS number120993-53-5
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor the treatment of heparin-induced thrombocytopenia
PharmacodynamicsLepirudin is used to break up clots and to reduce thrombocytopenia. It binds to thrombin and prevents thrombus or clot formation. It is a highly potent, selective, and essentially irreversible inhibitor of thrombin and clot-bond thrombin. Lepirudin requires no cofactor for its anticoagulant action. Lepirudin is a recombinant form of hirudin, an endogenous anticoagulant found in medicinal leeches.
Mechanism of actionLepirudin forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen and initiate the clotting cascade. The inhibition of thrombin prevents the blood clotting cascade.
AbsorptionBioavailability is 100% following injection.
Volume of distribution
  • 12.2 L [Healthy young subjects (n = 18, age 18-60 years)]
  • 18.7 L [Healthy elderly subjects (n = 10, age 65-80 years)]
  • 18 L [Renally impaired patients (n = 16, creatinine clearance below 80 mL/min)]
  • 32.1 L [HIT patients (n = 73)]
Protein bindingNot Available
Metabolism

Lepirudin is thought to be metabolized by release of amino acids via catabolic hydrolysis of the parent drug. However, con-clusive data are not available. About 48% of the administration dose is excreted in the urine which consists of unchanged drug (35%) and other fragments of the parent drug.

Route of eliminationLepirudin is thought to be metabolized by release of amino acids via catabolic hydrolysis of the parent drug. About 48% of the administration dose is excreted in the urine which consists of unchanged drug (35%) and other fragments of the parent drug.
Half lifeApproximately 1.3 hours
Clearance
  • 164 ml/min [Healthy 18-60 yrs]
  • 139 ml/min [Healthy 65-80 yrs]
  • 61 ml/min [renal impaired]
  • 114 ml/min [HIT (Heparin-induced thrombocytopenia)]
ToxicityIn case of overdose (eg, suggested by excessively high aPTT values) the risk of bleeding is increased.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Lepirudin Action PathwayDrug actionSMP00278
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
Manufacturers
  • Bayer healthcare pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous
Prices
Unit descriptionCostUnit
Refludan 50 mg vial273.19USDvial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States51806681993-01-192010-01-19
Canada13391041997-07-292014-07-29
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point65 °COtto, A. & Seckler, R. Eur. J. Biochem. 202:67-73 (1991)
hydrophobicity-0.777Not Available
isoelectric point4.04Not Available
References
Synthesis ReferenceNot Available
General Reference
  1. Smythe MA, Stephens JL, Koerber JM, Mattson JC: A comparison of lepirudin and argatroban outcomes. Clin Appl Thromb Hemost. 2005 Oct;11(4):371-4. Pubmed
  2. Tardy B, Lecompte T, Boelhen F, Tardy-Poncet B, Elalamy I, Morange P, Gruel Y, Wolf M, Francois D, Racadot E, Camarasa P, Blouch MT, Nguyen F, Doubine S, Dutrillaux F, Alhenc-Gelas M, Martin-Toutain I, Bauters A, Ffrench P, de Maistre E, Grunebaum L, Mouton C, Huisse MG, Gouault-Heilmann M, Lucke V: Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin. Blood. 2006 Sep 1;108(5):1492-6. Epub 2006 May 11. Pubmed
  3. Lubenow N, Eichler P, Lietz T, Greinacher A: Lepirudin in patients with heparin-induced thrombocytopenia – results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3. J Thromb Haemost. 2005 Nov;3(11):2428-36. Pubmed
  4. Askari AT, Lincoff AM: Antithrombotic Drug Therapy in Cardiovascular Disease. 2009 Oct; pp. 440–. ISBN 9781603272346. Google books.
External Links
ResourceLink
UniProtP01050
PharmGKBPA450195
Drug Product Database2240996
RxListhttp://www.rxlist.com/cgi/generic/lepirudin.htm
Drugs.comhttp://www.drugs.com/cdi/lepirudin.html
WikipediaLepirudin
ATC CodesB01AE02
AHFS Codes
  • 20:12.04.12
PDB Entries
FDA labelshow(128 KB)
MSDSshow(567 KB)
Interactions
Drug Interactions
Drug
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, Lepirudin. Monitor for increased bleeding during concomitant thearpy.
Food InteractionsNot Available

Targets

1. Prothrombin

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prothrombin P00734 Details

References:

  1. Turpie AG: Anticoagulants in acute coronary syndromes. Am J Cardiol. 1999 Sep 2;84(5A):2M-6M. Pubmed
  2. Warkentin TE: Venous thromboembolism in heparin-induced thrombocytopenia. Curr Opin Pulm Med. 2000 Jul;6(4):343-51. Pubmed
  3. Eriksson BI: New therapeutic options in deep vein thrombosis prophylaxis. Semin Hematol. 2000 Jul;37(3 Suppl 5):7-9. Pubmed
  4. Fabrizio MC: Use of ecarin clotting time (ECT) with lepirudin therapy in heparin-induced thrombocytopenia and cardiopulmonary bypass. J Extra Corpor Technol. 2001 May;33(2):117-25. Pubmed
  5. Szaba FM, Smiley ST: Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo. Blood. 2002 Feb 1;99(3):1053-9. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on May 12, 2013 21:37