Clinical pharmacology and mode of action of a new antithrombotic compound: Defibrotide.

Defibrotide is a derivative of polydeoxyribonucleotide extracted from bovine lung. Defibrotide has been found to modulate endothelial cell function causing increase in t-PA production and release with correction the defect in Cuff test in vascular disorders. Defibrotide causes a significant elevation in the PGI2 formation. In addition increase of platelet c-AMP levels with a decrease of MDA and TXA2 formation has been shown in human subjects. Defibrotide causes an inhibition of platelet activation were demonstrated with surface activation method as well ultrastructurally. Besides, an increase of protein C and FV were observed, a synergic action with heparin was observed. A strong antithrombotic effect has been shown in animal models and unlike most antithrombotic drugs defibrotide did not cause any effect of clotting tests in animals and human subjects. All findings support our earlier suggestion that defibrotide mainly acts via the modulation of endothelial cell function and acts as a novel fashion in contrast to the other drugs used in this area.