In vitro effect of the potent poly(ADP-ribose) polymerase (PARP) inhibitor INO-1001 alone and in combination with aspirin, eptifibatide, tirofiban, enoxaparin or alteplase on haemostatic parameters

Orsolya Tóth, Csaba Szabo, Marianna Kecskés, László Pótó, Ágnes Nagy, Hajna Losonczy

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

It has been shown that PARP inhibition is protective in several models of ischemia-reperfusion injury including cardiac, cerebral and renal ones. Due to their ability to reduce myocardial necrosis and to improve myocardial function PARP inhibitors emerged as candidates for treating various cardiovascular diseases including acute myocardial ischemia. Since the pathophysiology of acute ischemic cardiac diseases involves haemostatic impairment and the therapeutic regimen includes antithrombotic drugs, we investigated the effect of the potent poly(ADP-ribose) polymerase (PARP) inhibitor INO-1001 alone and in combination with platelet aggregation inhibitors (aspirin, eptifibatide and tirofiban), unfractionated heparin, low molecular weight heparin (enoxaparin) or the recombinant fibrinolytic drug (alteplase), on various haemostatic parameters in vitro. ADP- and epinephrine-induced platelet aggregation was evaluated by optical aggregometry in the presence or absence of different concentrations of INO-1001, in combination with aspirin, tirofiban, eptifibatide or saline on ten healthy volunteers' platelet rich plasma (PRP). Activated partial thromboplastin time, Anti-Xa activity and euglobulin lysis time were determined in the presence or absence of different concentrations of INO-1001, in combination with sodium heparin, enoxaparin or alteplase, respectively. INO-1001, on its own does not affect the measured platelet, and haemostatic functions, i.e. does not reduce the respective anti-platelet, anti-coagulant and thrombolytic activity of therapeutically relevant concentrations of aspirin, tirofiban, eptifibatide, enoxaparin and alteplase in vitro. INO-1001 enhanced the effects of heparins above therapeutic ranges; the magnitude of this effect was negligible. Consequently, the PARP inhibitor INO-1001 can be safely applied together with the drugs tested.

Original languageEnglish (US)
Pages (from-to)317-323
Number of pages7
JournalLife Sciences
Volume79
Issue number4
DOIs
StatePublished - Jun 20 2006
Externally publishedYes

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tirofiban
Enoxaparin
Tissue Plasminogen Activator
Hemostatics
Aspirin
Platelets
Heparin
Blood Platelets
Fibrin Clot Lysis Time
Serum Globulins
Coagulants
Platelet-Rich Plasma
Fibrinolytic Agents
Partial Thromboplastin Time
Poly(ADP-ribose) Polymerases
Low Molecular Weight Heparin
Platelet Aggregation Inhibitors
Thromboplastin
Reperfusion Injury
Platelet Aggregation

Keywords

  • Antithrombotic therapy
  • Drug interaction
  • Myocardial ischemia
  • PARP inhibitor

ASJC Scopus subject areas

  • Pharmacology

Cite this

In vitro effect of the potent poly(ADP-ribose) polymerase (PARP) inhibitor INO-1001 alone and in combination with aspirin, eptifibatide, tirofiban, enoxaparin or alteplase on haemostatic parameters. / Tóth, Orsolya; Szabo, Csaba; Kecskés, Marianna; Pótó, László; Nagy, Ágnes; Losonczy, Hajna.

In: Life Sciences, Vol. 79, No. 4, 20.06.2006, p. 317-323.

Research output: Contribution to journalArticle

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