| Primary information |
|---|
| ThPP ID | Th1001 |
| Therapeutic Peptide/Protein Name | Lepirudin |
| Sequence | LVYTDCTESGQNLCLCEGSNVCGQGNKCILGSDGEKNQCVTGEGTPKPQS view full sequnce in fasta |
| Functional Classification | Ia |
| Molecular Weight | 6963.425 |
| Chemical Formula | C287H440N80O110S6 |
| Isoelectric Point | 4.04 |
| Hydrophobicity | -0.777 |
| Melting Point (℃) | 65 |
| Half Life | Approximately 1.3 hours |
| 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. |
| Indication/Disease | 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. |
| Toxicity | In case of overdose (eg, suggested by excessively high aPTT values) the risk of bleeding is increased. |
| Metabolism | Lepirudin 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%) |
| Absorption | Bioavailability is 100% following injection. |
| Volume of Distribution | 12.2 L [Healthy young subjects (n = 18, age 18-60 years)] |
| Clearance | 164 ml/min [Healthy 18-60 yrs] |
| Categories | Antithrombins and Fibrinolytic Agents |
| Patents Number | CA1339104 |
| Date of Issue | 29/07/97 |
| Date of Expiry | 29/07/14 |
| Drug Interaction | Ginkgo biloba = may increase bleed risk. |
| Target | Prothrombin |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Refludan |
| Company | Berlex Labs |
| Brand Discription | REFLUDAN [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 for | heparin-induced thrombocytopenia (HIT) and associated thromboembolic disease |
| Chemical Name | [Leu1, Thr2]-63-desulfohirudin |
| Formulation | Each 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 Appearnce | Sterile, white, freeze-dried powder |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | Recommended 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. |
| Contraindication | Hypersensitivity |
| Side Effects | N.A. |
| Useful Link | http://www.drugs.com/pro/refludan.html |
| PubMed ID | 17381384, 16690967, 16553503, 16466327, 16370917, 16241940 |
| 3-D Structure | Th1001 (View) or (Download) |