Numerous comparison test was carried out for platelet aggregation, thrombus weight and bleeding time at each time point working with the automobile group as handle. In platelet transfusion experiments, a t-test was performed for the prasugrel and ticagrelor groups with no platelet transfusion employing the vehicle group as a handle, and was also performed between the groups with and with out platelet transfusion in prasugrel- and ticagrelortreated rats. In all analyses, statistical significance was defined as P 0.05. IC50, ED50 and ED200 values were calculated in the regression line for dose esponse relationship for inhibition of platelet aggregation, thrombus weight and bleeding time for every single test post. SAS eight.two and 9.2 for Windows (SAS Institute Inc., Cary, NC, USA) and EXSUS Ver. 7.1.6 and 7.7.1 (Arm Systex Co., Ltd., Osaka, Japan) or GraphPad Prism five (GraphPad Computer software Inc., La Jolla, CA, USA) have been applied to test significance and calculate ED50 or IC50 values.and 674 for 20 mmol -1 ADP. R-138727 (prasugrel’s active metabolite, 0.3000 mmol -1), ticagrelor (0.03030 mmol -1) and AR-C124910XX (ticagrelor’s active metabolite, 0.0300 mmol -1) inhibited ADP- (five and 20 mmol -1) induced platelet aggregation within a concentration-related manner. The IC50 values (with 95 self-confidence intervals) are summarized in Table 1. In the present study, the in vitro impact of prasugrel was not tested due to the fact prasugrel is usually a prodrug and thus has no in vitro effect on platelet aggregation (Sugidachi et al., 2000).Time course of ex vivo platelet aggregation induced by ADPEx vivo platelet aggregation was employed to measure the effects of single oral doses of prasugrel and ticagrelor on platelet aggregation induced by 5 and 20 mmol -1 ADP and were determined in blood samples taken at 1, two, four, eight, 12 and 24 h immediately after administration.Bryostatin 1 site For platelet aggregation induced by 20 mmol -1 ADP, single oral administration of prasugrel (0.Texas Red Fluorescent Dye 33 mg g-1) caused dose-related inhibitory effects (Figure 1A).PMID:23907521 With 1 and 3 mg g-1 of prasugrel, considerable inhibition was observed from 1 to 2 h soon after dosing. This inhibitory effect peaked at four h and lasted for 24 h soon after dosing, indicating a extended duration of action by prasugrel. Single oral administration of ticagrelor (ten mg g-1) also brought on dose-related inhibitory effect on platelet aggregation (Figure 1B). Ticagrelor, in the highest dose (ten mg g-1) considerably inhibited platelet aggregation at 1 h following dosing along with the peak inhibition was observed at four h after dosing. The inhibitory effect on platelet aggregation lasted for 12 h right after the dosing, but had returned to handle values by 24 h, indicating a shorter duration of antiplatelet action than that of prasugrel. For platelet aggregation induced by five mmol -1 ADP, equivalent time courses of inhibition of platelet aggregation had been observed for both prasugrel- and ticagrelor-treated rats (information not shown), even though the level of inhibition of platelet aggregation was slightly greater compared with that observed with 20 mmol -1 ADP. The ED50 values for prasugrel and ticagrelor at four h following the dosing were 1.5 mg g-1 and six.0 mg g-1, respectively, for 5 mmol -1 ADP and 1.9 mg g-1 and 8.0 mg g-1, respectively, for 20 mmol -1 ADP.MaterialsPrasugrel hydrochloride and R-138727 had been synthesized by Ube Industries, Ltd. (Yamaguchi, Japan). Ticagrelor was synthesized by Chemtech Labo, Inc. (Tokyo, Japan). AR-C124910XX was synthesized by Daiichi Sankyo RD Novare Co., Ltd. (Tokyo, Japan). Prasugrel and ticagrelor have been.