1. Pharmacodynamic effects during the transition between cangrelor and ticagrelor.
- Author
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Schneider DJ, Agarwal Z, Seecheran N, Keating FK, and Gogo P
- Subjects
- Adenosine administration & dosage, Adenosine Monophosphate administration & dosage, Administration, Oral, Aged, Blood Platelets metabolism, Cell Adhesion Molecules blood, Coronary Artery Disease blood, Coronary Artery Disease diagnosis, Drug Administration Schedule, Drug Interactions, Female, Humans, Infusions, Intravenous, Male, Microfilament Proteins blood, Middle Aged, Phosphoproteins blood, Phosphorylation, Platelet Aggregation drug effects, Platelet Function Tests, Receptors, Purinergic P2Y12 blood, Receptors, Purinergic P2Y12 drug effects, Ticagrelor, Time Factors, Vermont, Vasodilator-Stimulated Phosphoprotein, Adenosine analogs & derivatives, Adenosine Monophosphate analogs & derivatives, Blood Platelets drug effects, Coronary Artery Disease drug therapy, Drug Substitution, Platelet Aggregation Inhibitors administration & dosage, Purinergic P2Y Receptor Antagonists administration & dosage
- Abstract
Objectives: 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., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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