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Identification
Name Lepirudin
Accession Number DB00001 (BIOD00024, BTD00024)
Type biotech
Groups approved
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 structure Db00001
Display: 3D Structure
Protein chemical formula C287H440N80O110S6
Protein average weight 6963.4250
Sequences 
>DB00001 sequence
LVYTDCTESGQNLCLCEGSNVCGQGNKCILGSDGEKNQCVTGEGTPKPQSHNDGDFEEIP
EEYLQ

FASTA
Synonyms
Hirudin variant-1
Salts Not Available
Brand names
Name Company
Refludan Berlex Labs
Brand mixtures Not Available
Categories
  • Anticoagulants
  • Antithrombotic Agents
  • Fibrinolytic Agents
CAS number 120993-53-5
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For the treatment of heparin-induced thrombocytopenia
Pharmacodynamics Lepirudin 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 action Lepirudin 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.
Absorption Bioavailability 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 binding Not 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 elimination Lepirudin 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 life Approximately 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)]
Toxicity In case of overdose (eg, suggested by excessively high aPTT values) the risk of bleeding is increased.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00278 Lepirudin Pathway SMP00278
Pharmacoeconomics
Manufacturers
  • Bayer healthcare pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Prices
Unit description Cost Unit
Refludan 50 mg vial 273.19 USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 5180668 1993-01-19 2010-01-19
Canada 1339104 1997-07-29 2014-07-29
Properties
State liquid
Experimental Properties
Property Value Source
melting point 65 °C Otto, A. & Seckler, R. Eur. J. Biochem. 202:67-73 (1991)
hydrophobicity -0.777 Not Available
isoelectric point 4.04 Not Available
References
Synthesis Reference Not 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
Resource Link
UniProt P01050 Link_out
PharmGKB PA450195 Link_out
Drug Product Database 2240996 Link_out
RxList http://www.rxlist.com/cgi/generic/lepirudin.htm Link_out
Drugs.com http://www.drugs.com/cdi/lepirudin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Lepirudin Link_out
ATC Codes
  • B01AE02
AHFS Codes
  • 20:12.04.12
PDB Entries
FDA label show (128 KB)
MSDS show (567 KB)
Interactions
Drug Interactions
Drug Interaction
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Treprostinil The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the anticoagulant, Lepirudin. Monitor for increased bleeding during concomitant thearpy.
Food Interactions Not Available
Targets

1. Prothrombin

Pharmacological action: yes
Actions: inhibitor

Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C

Organism class: human
UniProt ID: P00734 Link_out
Gene: F2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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