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The Pharmacology and Clinical Pharmacology of Defibrotide: A New Profibrinolytic, Antithrombotic and Anti-Platelet Substance

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Fibrinogen, Thrombosis, Coagulation, and Fibrinolysis

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 281))

Abstract

Defibrotide, a deoxypolyribonuclide, has been found to modulate endothelial cell function causing increase in t-PA and decrease in PAI levels and also increase in PGI2 production. In addition, it increases platelet c-AMP levels and decreases MDA and TXB2 formation in human. Defibrotide inhibits platelet aggregate formation in vitro experiments as well as end-to-end anostomosis in rats. So, defibrotide inhibits the activation of platelets. Besides an increase of protein C and S levels a synergic action of heparin was observed in animal experiments. A strong antithrombotic effect has been observed in animal models.

The drug has a beneficial effect in the cases of DVT, POVD, stroke and thromboembolism. Through its action we may say that the drug acts in a novel fashion in contrast to the other drugs used in this area.

Defibrotide is a single-stranded polydeoxyribonucleotide obtained from deoxyribonucleic acid of mammalian lungs by controlled depolimerization. Since 1981 in our laboratory and in the clinical department we have been investigating a newly developed agent defibrotide in vitro experiments, animal experiments, and also its clinical pharmacology and clinical application.

Some of our findings are already published and compared with literature (40, 43, 46). Because of the limited space we are not going to review the literature in detail but we are going to summarize our observations on this compound in the following order. I — in vitro experiments, II — Animal experiments, III — clinical pharmacology in human.

Haemostasis and Thrombosis Research Center is affiliated with the Technical and Scientific Research Council of Turkey.

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Authors and Affiliations

  1. Haemostasis and Thrombosis Research Center, Cerrahpasa Medical School of Istanbul University, Istanbul, Turkey

    O. N. Ulutin, S. Balkuv-Ulutin, M. S. Ugur, T. Ulutin, Y. Özsoy & G. Çizmeci

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  1. O. N. Ulutin
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  2. S. Balkuv-Ulutin
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  3. M. S. Ugur
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  4. T. Ulutin
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  5. Y. Özsoy
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  6. G. Çizmeci
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Editor information

Editors and Affiliations

  1. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China

    Chung Yuan Liu

  2. University of California, San Diego, La Jolla, California, USA

    Shu Chien

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Ulutin, O.N., Balkuv-Ulutin, S., Ugur, M.S., Ulutin, T., Özsoy, Y., Çizmeci, G. (1990). The Pharmacology and Clinical Pharmacology of Defibrotide: A New Profibrinolytic, Antithrombotic and Anti-Platelet Substance. In: Liu, C.Y., Chien, S. (eds) Fibrinogen, Thrombosis, Coagulation, and Fibrinolysis. Advances in Experimental Medicine and Biology, vol 281. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3806-6_46

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  • DOI: https://doi.org/10.1007/978-1-4615-3806-6_46

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