Transitioning patients from cangrelor to clopidogrel: pharmacodynamic evidence of a competitive effect.
BACKGROUND
Cangrelor is a direct, parenteral, and reversible inhibitor of the platelet P2Y12 receptor currently undergoing Phase III testing. As many individuals treated acutely with cangrelor will often be treated long-term with a thienopyridine, it is important to determine the effects of concurrent cangrelor and clopidogrel administration.


RESULTS
Ten healthy volunteers received a 600 mg oral loading dose of clopidogrel and then underwent serial platelet function monitoring for 6 h. Two weeks later these same individuals received a 600 mg clopidogrel loading dose simultaneously with a cangrelor IV bolus (30 microg/kg) and a 2-hour infusion (4 microg/kg/min). A separate group of ten volunteers received a 600 mg clopidogrel loading dose after administration of a cangrelor bolus and a 1-hour infusion. The effects on ADP-induced platelet activation and aggregation were evaluated by flow cytometry, whole-blood electrical impedance, and light-transmittance aggregometry. Cangrelor and clopidogrel alone achieved the expected levels of platelet inhibition. However, the sustained platelet inhibition anticipated for clopidogrel treatment did not occur when cangrelor was initiated simultaneously. No such effect was found when clopidogrel was started upon completion of the cangrelor infusion.


CONCLUSIONS
To achieve sustained platelet P2Y12 inhibition in patients treated with cangrelor, clopidogrel administration should be started when the cangrelor infusion is terminated.
Steinhubl
Steven R
SR
Division of Cardiology, Department of Pharmacy Practice and Science, University of Kentucky, Lexington, Kentucky 40536-0200, USA. steinhubl@uky.edu
Oh
Jennifer J
JJ
Oestreich
Julie H
JH
Ferraris
Suellen
S
Charnigo
Richard
R
Akers
Wendell S
WS
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000077144:Clopidogrel; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D019007:P-Selectin; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; C117446:cangrelor; D000077144:Clopidogrel; D013988:Ticlopidine