Antithrombotic action of recombinant hirudin in a venous thrombosis model.
The dose- and time-dependent antithrombotic activity of recombinant hirudin (r-hirudin) was examined in a new animal model of venous thrombosis. For the evaluation of the antithrombotic activity of r-hirudin, an occluding thrombus was produced by repeated clamping of the rat jugular vein. The number of clampings necessary to induce thrombosis served as a measure of antithrombotic activity. The gradual reduction of blood flow was registered by Doppler sonography. In order to estimate the relative antithrombotic activity of r-hirudin, its potency in this model was compared with other antithrombotic substances. r-Hirudin proved to be less potent than heparin after intravenous administration. Its half-life after subcutaneous administration was relatively short; however, the antithrombotic potency after subcutaneous administration was comparable to that of heparin.
Raake
W
W
Department of Pharmacology and Chemistry, Luitpold-Werk, Munich, FRG.
Klauser
R J
RJ
Elling
H
H
Zeiller
P
P
D000818:Animals; D001780:Blood Coagulation Tests; D003250:Constriction; D004187:Disaccharides / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage / Q000633:toxicity; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007601:Jugular Veins / Q000293:injuries; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D013623:Tail; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*
D004187:Disaccharides; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D011994:Recombinant Proteins; D006493:Heparin; C069690:aprosulate