Ing time measurements. Outcomes are presented as the imply + SEM (n = 10). V = car control. **P 0.01, significantly distinct from vehicle group (Dunnett’s test). 86 British Journal of Pharmacology (2013) 169 82?A 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 prior to bleeding time measurements. Platelets (Plt) were infused i.v. 1 h just before bleeding time measurements. Bleeding occasions are shown because the implies + SEM (n = 13?four). Plt, platelets; NS, not significant (t-test).ticagrelor and AR-C124910XX would have approximately equivalent effects on in vivo platelet inhibition following ticagrelor dosing. In the present study, prasugrel’s active metabolite (R-138727) inhibited in vitro platelet aggregation, and its in vitro antiplatelet activity was significantly 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 much more potent than ticagrelor on ex vivo platelet aggregation induced by ADP. Moreover, we identified prasugrel’s inhibition of ex vivo platelet aggregation was sustained for as much as 24 h immediately after the administration, while ticagrelor demonstrated a shorter duration of action and also the antiplatelet effect was lost 24 h soon after dosing. Attainable explanations for these differences in between in vitro and ex vivo effects could be as a result of variations 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 your longer duration of antiplatelet action. Additionally, a recent report showed that ticagrelor may have effects on adenosine transporters in human platelets, which might contribute to its antiplatelet action (Iy?et al., 2011). Thus, inhibition of adenosine transporters may possibly contribute for the additional potent in vitro activity of ticagrelor. Nevertheless, a different report recommended that any impact of ticagrelor on adenosine uptake was not adequate to amplify the antiplatelet effects of any adenosine generated inside the presence of P2Y12 receptor antagonists (van Giezen et al.945652-35-7 custom synthesis , 2012).(6-Bromopyridin-2-yl)methanamine Chemscene In addition, the ADP concentration/response aggregation profiles of prasugrel and ticagrelor were compared at peak inhibition of platelet aggregation, and identified to become related with each agents, as previously reported (Sugidachi et al.PMID:23290930 , 2000; van Giezen et al., 2009), acting as noncompetitive antagonists. Antithrombotic therapy is often a cornerstone of therapy in sufferers with cardiovascular disease with bleeding being themost worrisome complication. Indeed, while prasugrel and ticagrelor deliver greater inhibition of platelet aggregation and clinical efficacy than clopidogrel, both agents have been linked with far more bleeding compared with clopidogrel (Wiviott et al., 2007; Becker et al., 2011). Inside the present study, the connection among antiplatelet, antithrombotic and bleeding activities of both prasugrel and ticagrelor had been compared in rats. Both agents inhibited platelet aggregation, thrombus formation and haemostasis within a dose-related manner having a related potency ratio of about four times amongst all of the parameters tested in the time of peak inhibition of platelet aggregation (4h). These data recommend that at equivalent.
