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1001 details
Primary information
ThPP IDTh1001
Therapeutic Peptide/Protein NameLepirudin
SequenceLVYTDCTESGQNLCLCEGSNVCGQGNKCILGSDGEKNQCVTGEGTPKPQS view full sequnce in fasta
Functional ClassificationIa
Molecular Weight6963.425
Chemical FormulaC287H440N80O110S6
Isoelectric Point4.04
Hydrophobicity-0.777
Melting Point (℃)65
Half LifeApproximately 1.3 hours
DescriptionLepirudin 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.
Indication/DiseaseFor 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.
ToxicityIn case of overdose (eg, suggested by excessively high aPTT values) the risk of bleeding is increased.
MetabolismLepirudin is thought to be metabolized by release of amino acids via catabolic hydrolysis of the parent drug. However, conclusive data are not available. About 48% of the administration dose is excreted in the urine which consists of unchanged drug (35%)
AbsorptionBioavailability is 100% following injection.
Volume of Distribution12.2 L [Healthy young subjects (n = 18, age 18-60 years)]
Clearance164 ml/min [Healthy 18-60 yrs]
CategoriesAntithrombins and Fibrinolytic Agents
Patents NumberCA1339104
Date of Issue29/07/97
Date of Expiry29/07/14
Drug InteractionGinkgo biloba = may increase bleed risk.
TargetProthrombin
Information of corresponding available drug in the market
Brand NameRefludan
CompanyBerlex Labs
Brand DiscriptionREFLUDAN [lepirudin (rDNA) for injection] is a highly specific direct inhibitor of thrombin. It is a recombinant hirudin derived from yeast cells. The polypeptide composed of 65 amino acids. Natural hirudin is produced in trace amounts as a family of high
Prescribed forheparin-induced thrombocytopenia (HIT) and associated thromboembolic disease
Chemical Name[Leu1, Thr2]-63-desulfohirudin
FormulationEach vial of REFLUDAN contains 50 mg lepirudin. Other ingre-dients are 40 mg mannitol and sodium hydroxide for adjust-ment of pH to approximately 7
Physcial AppearnceSterile, white, freeze-dried powder
Route of AdministrationIntravenous infusion
Recommended DosageRecommended dose is 0.4 mg/kg body weight (up to 110kg) slowly intravenously (eg, over 15 to 20seconds) as a bolus dose, and can be followed by 0.15 mg/kg body weight (up to 110kg)/hour as a continuous Intravenous infusion for 2 to 10 days or longer if CL.
ContraindicationHypersensitivity
Side EffectsN.A.
Useful Linkhttp://www.drugs.com/pro/refludan.html
PubMed ID17381384, 16690967, 16553503, 16466327, 16370917, 16241940
3-D StructureTh1001 (View) or (Download)