M to generate an active metabolite, AR-C124910XX (Teng and Butler, 2010), but in contrast towards the thienopyridines, both the parent drug and active metabolite exhibit platelet inhibitory activity (van Giezen and Humphries, 2005; Teng and Butler, 2010). Pharmacological assessment of treatment with ticagrelor ought to thus contemplate the pharmacokinetics and pharmacodynamics of both ticagrelor and its active metabolite. Each prasugrel and ticagrelor had been extra successful than clopidogrel and might thus be preferred in ACS patients. Even so, to date, no large-scale clinical study has straight compared the efficacy and safety of prasugrel and ticagrelor (Alber et al., 2011), though a smaller clinical pharmacology study in ACS sufferers with higher on-treatment platelet reactivity (Alexopoulos et al., 2012) and an adjusted indirect meta-analysis comparing each agents (Biondi-Zoccai et al., 2011) have already been reported. Moreover, there’s, so far, no detailed non-clinical comparison from the pharmacological profile of prasugrel and ticagrelor. Within the present study, we determined the relative pharmacological profiles of your anti-platelet activities of prasugrel and ticagrelor, making use of experimental models in rats, and found quite a few variations. To our expertise, that is the initial formal, detailed non-clinical study to compare the pharmacological profiles of those novel P2Y12 receptor antagonists.Shizuoka, Japan; 7 weeks old at receipt) were utilized inside the present study. Rats were housed in animal quarters set at a continual temperature, humidity and 12 h light/dark cycle.Mouse IgG2b kappa, Isotype Control Autophagy Rats have been maintained with absolutely free access to water and food and employed after an acclimatization period of at the least six days.Preparation of platelet-rich plasma (PRP) and platelet-poor plasma (PPP)In ex vivo studies, blood was collected from the abdominal aorta under anaesthesia with pentobarbital sodium (35 mg g-1, i.p.) at 1, 2, four, 8, 12 and 24 h following the administration on the test agent. four.five mL of blood was drawn into a disposable syringe containing 0.5 mL of three.eight sodium citrate (pH 7.four). For in vitro research, six mL of blood was collected in a related manner. The anti-coagulated blood was centrifuged (15000g for ten min at area temperature) to obtain PRP.OBAA Protocol Right after getting PRP, the remaining blood was centrifuged (1300500g for 15 min at space temperature) to obtain PPP.PMID:23554582 Platelet counts inside the PRP had been obtained making use of an automated blood cell counter (F-800 or XT-2000 iV, Sysmex Corporation, Hyogo, Japan), and PRP containing 50 five 104 platelets L-1 was prepared by diluting with PPP.Platelet aggregationIn the in vitro studies, PRP was incubated using the vehicle or the test agents for 30 min at space temperature prior to measuring aggregation to ADP. Within the ex vivo research, 240 mL on the PRP prepared was stirred for 1 min at 37 , and 10 mL of agonist (ADP or collagen) was subsequently added to induce platelet aggregation. Platelet aggregation was monitored for ten min following agonist addition and recorded as maximum platelet aggregation making use of a 12-channel automated platelet aggregometer (MCM HEMA TRACER 313 or 712, MC Medical, Inc., Tokyo, Japan).Arterio-venous (AV) shunt thrombosis modelThe potential on the agents to prevent thrombus formation was assessed working with an AV shunt model described previously by Sugidachi et al. (2000) with slight modifications. Right after anaesthesia with pentobarbital sodium (50 mg g-1, i.p.), the jugular vein and contralateral carotid artery of rats have been exposed and were cannulated with a tube.
