About KENGREAL® (cangrelor)
Pathophysiology—Thrombosis after injury
Thrombotic response to laser-induced injury in mouse cremaster muscle arteriole performed in vitro.1-3
KENGREAL® is the first and only IV inhibitor that blocks platelet ADP activation and aggregation.1
Phase 1 study in healthy volunteers (n=10); dose: 30 μg/kg IV bolus + 4 μg/kg/min IV infusion.
Blood levels of KENGREAL® (green line/PK) and platelet activity (blue line/PD) were assessed over 6 minutes by whole blood impedance aggregometry in response to 20 μM of adenosine diphosphate (ADP).4
After administration of a 30 mcg/kg IV bolus followed by a 4 mcg/kg/min IV infusion, platelet inhibition occurs within 2 minutes. The figure above shows the effect on platelet activity, and its relation to KENGREAL® plasma concentration, of administering a 30 mcg/kg IV bolus, followed by a 1-hour 4 mcg/kg/min IV infusion of KENGREAL®. The antiplatelet effect is maintained for the duration of the infusion. After discontinuation of the infusion, the antiplatelet effect decreases rapidly and platelet function returns to normal within 1 hour.4
Developed for acute use in PCI†
|Compound class||ATP‡ analogue|
|Direct-acting, does not require metabolism||YES|
|Onset of PD effect||~2 min|
|Reversible P2Y12 receptor binding||YES|
|Offset of PD effect||~1 h|
|Clearance of active substance||Independent of organ function; esterases|
KENGREAL® administered intravenously has linear pharmacokinetics in both healthy volunteers and patients. KENGREAL® is rapidly distributed and metabolized, reaching Cmax within 2 minutes after administration of an intravenous bolus followed by infusion.
*The correlation of pharmacology or chemical class with clinical efficacy or safety results has not been established.
†KENGREAL® is a P2Y12 platelet inhibitor indicated as an adjunct to percutaneous coronary intervention (PCI) to reduce the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor.
References: 1. KENGREAL® (cangrelor) Prescribing Information. 2016. 2. Gachet C. J Thromb Haemost. 2015;13:S313-S322. 3. Stalker T, et al. Blood. 2013;121:1875-1885. 4. Akers WS, Oh JJ, Oestreich JH, Ferraris S, Wethington M, Steinhubl SR. Clin Pharmacol. 2010;50:27-35.