013) 169 82A comparison of pharmacological profiles of prasugrel and ticagrelorBJPFigureEffects of platelet transfusion on prolongation of bleeding time by prasugrel or ticagrelor in rats. Prasugrel and ticagrelor were orally administered 4 h just before bleeding time measurements. Platelets (Plt) have been infused i.v. 1 h prior to bleeding time measurements. Bleeding instances are shown because the suggests + SEM (n = 134). Plt, platelets; NS, not substantial (t-test).ticagrelor and AR-C124910XX would have roughly equivalent effects on in vivo platelet inhibition following ticagrelor dosing. Inside the present study, prasugrel’s active metabolite (R-138727) inhibited in vitro platelet aggregation, and its in vitro antiplatelet activity was much less potent than ticagrelor and AR-C124910XX. Nevertheless, as reported in clinical research (Jernberg et al., 2006; Gurbel et al., 2010), on a mg g-1 basis, orally administered prasugrel was more potent than ticagrelor on ex vivo platelet aggregation induced by ADP. Furthermore, we discovered prasugrel’s inhibition of ex vivo platelet aggregation was sustained for as much as 24 h after the administration, though ticagrelor demonstrated a shorter duration of action and the antiplatelet effect was lost 24 h just after dosing. Possible explanations for these differences among in vitro and ex vivo effects could possibly be due to differences in pharmacokinetic profiles and their different irreversible (Sugidachi et al., 2000; 2001) and reversible antiplatelet actions (Wijeyeratne et al., 2012). Irreversible inhibition of P2Y12 receptors by prasugrel can also be an explanation of the longer duration of antiplatelet action. In addition, a recent report showed that ticagrelor could have effects on adenosine transporters in human platelets, which may well contribute to its antiplatelet action (Iyet al.Anti-Mouse H-2K Antibody site , 2011).Bakuchiol p38 MAPK As a result, inhibition of adenosine transporters may well contribute towards the far more potent in vitro activity of ticagrelor. However, an additional report recommended that any effect of ticagrelor on adenosine uptake was not sufficient to amplify the antiplatelet effects of any adenosine generated inside the presence of P2Y12 receptor antagonists (van Giezen et al., 2012). Additionally, the ADP concentration/response aggregation profiles of prasugrel and ticagrelor were compared at peak inhibition of platelet aggregation, and found to be similar with each agents, as previously reported (Sugidachi et al.PMID:23514335 , 2000; van Giezen et al., 2009), acting as noncompetitive antagonists. Antithrombotic therapy is actually a cornerstone of remedy in sufferers with cardiovascular illness with bleeding becoming themost worrisome complication. Certainly, when prasugrel and ticagrelor deliver greater inhibition of platelet aggregation and clinical efficacy than clopidogrel, each agents have been associated with extra bleeding compared with clopidogrel (Wiviott et al., 2007; Becker et al., 2011). In the present study, the connection amongst antiplatelet, antithrombotic and bleeding activities of both prasugrel and ticagrelor were compared in rats. Both agents inhibited platelet aggregation, thrombus formation and haemostasis within a dose-related manner having a related potency ratio of about 4 times among all the parameters tested at the time of peak inhibition of platelet aggregation (4h). These information recommend that at equivalent levels of platelet inhibition, the two agents would show comparable antithrombotic activity with equivalent bleeding risk in spite of their distinct modes of actions at the P2Y12 receptor level, that may be reversible (.
