On The Pharmacology Of Hirudin

Hirudin, the anticoagulant substance obtained from medicinal leeches, was isolated and chemically characterized by us 20 years ago. In order to estimate the potential therapeutic effect, its pharmacodynamic and pharmacokinetic properties were studied in animal experiments. Pure hirudin is well tolerated and, except its anticoagulant effect, it proved to be a pharmacologically inert substance. According to its physico- chemical properties as a polypeptide ( MW 7600) it is not absorbed enterally in active form and does not penetrate the skin. After parenteral administration hirudin distributes in extracellular fluid. It is eliminated with a half-life of 70 min and 80 % are excreted in unchanged form through the kidneys.The specific inhibition of thrombin by hirudin in the blood prevents not only fibrinogen conversion but also the thrombin-catalyzed activation of other clotting factors and platelets. The antithrombotic effect was demonstrated in experimental animals (rat, rabbit, dog). The incidence of venous clotting thrombi induced by stasis and of arterial deposition thrombi induced by lesion of the vessel wall was prevented. Of special importance is the effect of hirudin to prevent microthrombosis in DIC induced by infusion of thrombin or endotoxin. In this case hirudin is superior to heparin.Pre-clinical testing showed that hirudin is a potential antithrombotic agent.