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Defibrotide Interactions with Anticoagulant Drugs. Developmental Implications.
Author(s) -
Hoppensteadt Debra,
Cunanan Josephine,
Clark Melanie,
Iqbal Omer,
Adiguzel Cafer,
Fareed Daniel,
Fareed Jawed
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1118.12
Subject(s) - antithrombin , pharmacology , chemistry , heparin , dose , anticoagulant , defibrotide , medicine , biochemistry , transplantation , hematopoietic stem cell transplantation
Defibrotide (D) is a mammalian polyelectrolyte/polyribonucleotide derived antithrombin agent with aptameric consensus antithrombin sequences. This agent is used in vascular system in both the intravenous and oral regimens. Since this drug is used in certain pathologic conditions where other anticoagulants such as heparin (H), low molecular weight heparins (LMWHs) and oral anticoagulants (OAC) are used, the potential interaction of this agent with these drugs needed an understanding of these processes. In order to investigate the potential interaction between D, H and OAC, plasma samples from patients treated with H at therapeutic dosages (n=100), (APTT=50–90 seconds): LMWHs (n=100), (Heptest= 60–90 seconds); and OAC (n=100), (PT= 18–25 seconds) were supplemented with graded dosages of D, 10–100 ug/ml. H showed a D concentration dependent synergistic interaction in terms of a 20–80% increase in the APTT, whereas this interaction was not sp obvious with Heptest and anti‐Xa. LMWHs at concentrations >0.3 U/ml also showed an interaction with D, however to a lesser magnitude that H. D did not show any strong interaction with OAC in terms of PT/INR measurements. In the thrombin generation assays D supplementation augmented the inhibition of protease generation. These results suggest that D can potentially interact with currently available anticoagulant drugs. Moreover, the interaction of this agent with newly developed antithrombin and anti‐Xa agents warrants additional studies.