Levels of platelet inhibition, the two agents would show similar antithrombotic activity with related bleeding threat regardless of their distinct modes of actions at the P2Y12 receptor level, that’s reversible (ticagrelor) or irreversible (prasugrel) antagonism. There are lots of reversal methods obtainable for individuals on antiplatelet therapy who present with an acute haemorrhage or demand urgent surgery, like platelet transfusion (Lemmer, 2000; McMillian and Rogers, 2009), although some potentially deleterious effects have been observed (Bassand, 2009). Indeed, Vilahur et al. (2007) reported that in vitro platelet concentrates could restore haemostatic possible inside the face of clopidogrel-induced platelet dysfunction. The present in vivo outcome showed that platelet transfusion considerably shortened prasugrel-induced prolongation of bleeding time in rats. In contrast, in ticagrelor-treated rats, platelet transfusion failed to reverse prolongation of bleeding time. This unexpected finding may possibly rely on the distinct reversibility profile and/or distinctive pharmacokinetic profile from the agent: It would appear that antiplatelet action of ticagrelor correlates with blood levels of ticagrelor and its active metabolite (Teng and Butler, 2010; Husted et al., 2012). Therefore, newly transfused platelets would be readily inhibited by the presence of no cost ticagrelor and/or its active metabolite in plasma. In contrast, prasugrel is definitely an irreversible antiplateletBritish Journal of Pharmacology (2013) 169 82?9BJPA Sugidachi et al.agent with only transient exposure of platelets to its active metabolite needed for sustained platelet inhibition. At 4 h after the dosing, when maximum inhibition of platelet aggregation was observed in rats, the blood concentration of prasugrel’s active metabolite is substantially lower than its peak (Cmax) level (Sugidachi et al., 2007; Hagihara et al., 2009), thereby permitting transfused platelets to stay functional and deliver haemostatic potential. In addition, this pharmacokinetic / pharmacodynamic connection in prasugrel-treated rats is related to that observed in humans (Jakubowski et al.159611-02-6 custom synthesis , 2007).Fmoc-1-Nal-OH Order In conclusion, both prasugrel and ticagrelor inhibited platelet aggregation and thrombus formation although prolonging bleeding with a comparable potency ratio of around 4 instances among these activities. Furthermore, prasugrel showed longer duration of antiplatelet action compared with ticagrelor. The present study also recommended that ticagrelor and its active metabolite may possibly play equal roles in providing in vivo antiplatelet activity.PMID:23546012 Despite the fact that the platelet inhibitory effect of prasugrel was reversed by platelet transfusion, that of ticagrelor was not. The disparity in findings in between prasugrel- and ticagrelor-treated rats may perhaps reflect the distinct reversibility and/or pharmacokinetic profiles on the two agents.antagonists clopidogrel and ticagrelor within the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J 32: 2933?944. Biondi-Zoccai G, Lotrionte M, Agostoni P, Abbate A, Romagnoli E, Sangiorgi G et al. (2011). Adjusted indirect comparison meta-analysis of prasugrel versus ticagrelor for individuals with acute coronary syndromes. Int J Cardiol 150: 325?31. Dobesh PP (2009). Pharmacokinetics and pharmacodynamics of prasugrel, a thienopyridine P2Y12 inhibitor. Pharmacotherapy 29: 1089?102. van Giezen JJ, Humphries RG (2005). Preclinical and clinical research with selective reversible direct P2Y12 antagonists.