Investigation of the PADA as a method for monitoring GPIIb/IIIa inhibitors and other antiplatelet agents.
Treatment with glycoprotein (GP) IIb/IIIa inhibitors in combination with aspirin and clopidogrel have become essential therapeutic strategies during invasive procedures and coronary events. However, the ideal monitoring test for the effects of these treatments is still missing. Therefore, we investigated the new Platelet Adhesion Assay (PADA) for its sensitivity in characterizing antiplatelet therapy. Five healthy volunteers were studied before and after a single dose of aspirin (500 mg). Samples were spiked in vitro with increasing doses of abciximab (0, 0.25, 1, 3 microg/mL), eptifibatide (0, 0.25, 1, 2 microg/mL), and AR-C 69931 MX (1 microg/mL) in citrated and hirudinized whole blood. The adhesion index (AI), as the characteristic parameter of the PADA test, decreased in a dose-dependent fashion for abciximab and eptifibatide. Variable effects between the different anticoagulants were shown for eptifibatide. Aspirin showed no additional effect, while inhibition by AR-C 69931 MX was demonstrated in hirudinized blood only. We concluded that different levels of GPIIb/IIIa inhibitors and adenosine diphosphate-receptor inhibition could be assessed with the PADA test, although different anticoagulants led to different results. The suitability of this test for daily use will have to be elucidated in further patient studies.
Graff
Jochen
J
Institute of Clinical Pharmacology at the Pharmazentrum Frankfurt, University Hospital, Frankfurt am Main, Germany. graff@em.uni-frankfurt.de
Harder
Sebastian
S
D000077284:Abciximab; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D000077542:Eptifibatide; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010973:Platelet Adhesiveness; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests / Q000295:instrumentation* / Q000379:methods*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D012680:Sensitivity and Specificity; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D006629:Hirudins; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000249:Adenosine Monophosphate; C117446:cangrelor; D000077144:Clopidogrel; D000077542:Eptifibatide; D013988:Ticlopidine; D001241:Aspirin; D000077284:Abciximab