title: Pharmacodynamic effects during the transition between cangrelor and ticagrelor.
abstract: OBJECTIVE
  This study sought to determine pharmacodynamic effects during transition from intravenous cangrelor to oral ticagrelor and from oral ticagrelor to intravenous cangrelor.
  
  
  BACKGROUND
  Cangrelor is an intravenous antagonist of P2Y12 and its use will require transition to and from oral agents.
  
  
  METHODS
  Patients (n = 12) with stable coronary artery disease who were taking aspirin 81 mg daily were recruited. On study day 1, they received a bolus plus 2-h infusion of cangrelor plus a 180-mg dose of ticagrelor at either 0.5 h (n = 6) or 1.25 h (n = 6). Pharmacodynamic effects (light transmission platelet aggregation in response to 20 and 5 μmol/l adenosine diphosphate, VerifyNow, P2Y12 assay (Accumetrics, San Diego, California), vasodilator-stimulated phosphoprotein index, and flow cytometry) were assessed during and after the cangrelor infusion. Patients took 90 mg of ticagrelor twice daily for either 6 (n = 6) or 7 (n = 6) doses. On study day 5, pharmacodynamic effects were assessed before and during a bolus plus 2-h infusion of cangrelor.
  
  
  RESULTS
  During cangrelor infusion, extensive inhibition of platelet function reflected by limited residual platelet reactivity was apparent. After cangrelor was stopped, the antiplatelet effects of ticagrelor were preserved despite a modest increase in platelet reactivity.
  
  
  CONCLUSIONS
  Ticagrelor given before or during infusion of cangrelor did not attenuate the pharmacodynamic effects of cangrelor. The pharmacodynamic effects of ticagrelor were preserved when ticagrelor was given during infusion of cangrelor. Consistent with the reversible binding of ticagrelor, this oral P2Y12 antagonist can be administered before, during, or after treatment with cangrelor.
authors.affiliation: Cardiology Unit, and Cardiovascular Research Institute, Department of Medicine, University of Vermont, Burlington, Vermont. Electronic address: david.schneider@uvm.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Schneider
authors.affiliation: Cardiology Unit, and Cardiovascular Research Institute, Department of Medicine, University of Vermont, Burlington, Vermont.
authors.forename: Zubin
authors.initials: Z
authors.lastname: Agarwal
authors.affiliation: Cardiology Unit, and Cardiovascular Research Institute, Department of Medicine, University of Vermont, Burlington, Vermont.
authors.forename: Naveen
authors.initials: N
authors.lastname: Seecheran
authors.affiliation: Cardiology Unit, and Cardiovascular Research Institute, Department of Medicine, University of Vermont, Burlington, Vermont.
authors.forename: Friederike K
authors.initials: FK
authors.lastname: Keating
authors.affiliation: Cardiology Unit, and Cardiovascular Research Institute, Department of Medicine, University of Vermont, Burlington, Vermont.
authors.forename: Prospero
authors.initials: P
authors.lastname: Gogo
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000249:Adenosine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000284:Administration, Oral; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D057915:Drug Substitution; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage*; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D000077486:Ticagrelor; D013997:Time Factors; D014707:Vermont; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000249:Adenosine Monophosphate; C117446:cangrelor; D000077486:Ticagrelor; D000241:Adenosine
keywords: antiplatelet; cangrelor; pharmacodynamics; ticagrelor; transition