Hirudin derivatives

The prototype of this class is hirudin, which was originally isolated from the salivary glands of the medicinal leech, Hirudo medicinalis. Hirudin itself is not commercially available, but recombinant technology has permitted production of hirudin derivatives, namely lepirudin and desirudin.29,38,41 Lepirudin has a short half-life of approximately 40 minutes after IV administration and 120 minutes when given SC. Elimination of lepirudin is primarily renal therefore, doses must be adjusted based on the patient s renal function. The dose should be monitored and adjusted to achieve an aPTT ratio of 1.5 to 2.5 times the baseline measurement. Lepirudin is currently approved for use in patients with HIT and related thrombosis. Up to 40% of patients treated with lepirudin will develop antibodies to the drug.29,38,41... 

Pharmacology Lepirudin (rDNA), a recombinant hirudin derived from yeast cells, is a highly specific direct inhibitor of thrombin. 

In contrast direct-acting preparations have the ability to inhibit fibrin-bound thrombin and include hirudin derived from medicinal leeches but now produced by recombinant technology. Particular interest centres on ximelagatran which may be a possible... 

Chemical Class Hirudin derivative thrombin inhibitor... 

Another natural anticoagulant is hirudin, derived from the saliva of the leech (.hirudo is the Latin word for leech). Leeches, in fact, are still occasionally used themselves therapeutically for certain topical applications. Another possible drug to be used for the dissolution of blood clots is derived from bat saliva and acts as a... 

Lepirudin and desirudin have been approved for the treatment of HIT and of HIT with thrombotic syndrome (71). Both lepirudin and desirudin are recombinant hirudin derivatives that consists of a 65-amino-acid protein (72,73). Lepirudin is related to the recombinant product desirudin differing in the two N-terminal amino acids. The N-terminal amino acids in lepirudin are leucine-1 and threonine-2, whereas in desirudin, the N-terminal amino acids are valine-1 and valine-2. Additionally, desirudin lacks a sulfated tyrosine at amino acid 63. The antithrombin activity of the two drugs is slightly different. 

Hirudin is a polypeptide derived from the saliva of the leech Hirudo medicinalis that binds to the blood serine proteinase, thrombins, and thus blocks clot formation. 

Markwardt F. Hirudin and derivatives as anticoagulant agents, Thromb Haemost 1991 66, 141-52. 

Hirudin is a leech-derived anticoagulant that functions by directly inhibiting thrombin. A range of blood-sucking animals contain substances in their saliva that specifically inhibit some element of the blood coagulation system (Table 12.4). 

Stimulation by thrombin does not lead to the generation of leukotriene C4 or B4, whereas stimulation of the same mast cells by the calcium ionophore, A23187, does. The secretory response elicited by thrombin is prevented by preincubation with AT-III, a plasma inhibitor of thrombin, or by hirudin, a thrombin inhibitor derived from the leech [135],... 

Fitzgerald, G. (1996). The human pharmacology of thrombin inhibition. Coronary Artery Dis. 7(12), 911-918. Markwardt, F. (1991). Hirudin and its derivatives as anticoagulant agents. Thromb. Haemost. 66, 141-152. 

Lepirudin is a recombinant derivative of hirudin (direct thrombin inhibitor secreted by salivary glands of leech). It inhibits thrombin directly and is mainly used in heparin induced thrombocytopenia. 

A. General description Lepirudin is a recombinant hirudin, a highly specific direct inhibitor of thrombin, derived from yeast cells. The polypeptide is composed of 65 amino acids and has a molecular weight of 7 kD. Natural hirudin is produced in trace amounts as a family of highly homologous isopolypeptides by the medicinal leech. Lepirudin is identical to natural hirudin except for the substitution of leucine for isoleucine at the N-terminal end... 

A. General description Bivalirudin, a 20 amino-acid synthetic peptide, is a direct thrombin inhibitor. It is an analogue of recombinant hirudin (Refludan), a 65 amino-acid anticoagulant derived from the leech. The molecular weight of bivalirudin is about 2.2kDa (anhydrous free base peptide). 

Bivalirudin is a direct thrombin inhibitor that has found utility for reducing the rate of acute reocclusion in patients treated with PCI. It is preferential to heparin in PCI when HIT is present. This drug is a derivative of hirudin, which is a dedicated thrombin inhibitor with no other in vivo activities of significance. The molecule is semisynthetic the C-terminal of hirudin is linked by a polyglycine spacer to the tetrapeptide region of the N-terminal that reacts with the thrombin active site (22). It is monitored by the activated clotting time test. Its pharmacologic properties are shown in Table I. 

Hirudin is a direct thrombin inhibitor marketed in a recombinant form (lepirudin). It is a protein derived from a salivary gland of the medicinal leech. It binds tightly to exosite I and the apolar site near the catalytic site. It is used as a substitute for... 

Hirudin and its derivatives (bivalirudin, lepirudin) block the active center of thrombin. 

The polypeptide hirudin from the saliva of the European medicinal leech inhibits clotting of the leech s blood meal by blockade of the active center of thrombin. This action is independent of AT III and thus also occurs in patients with AT III deficiency. Lepirudin and desrudin are yeast-derived recombinant analogues. They can be used in patients with HIT II. 

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