MD-1

We aimed to characterize platelet aggregation responses and the impact of dual antiplatelet therapy in microminipigs. In this in vitro study, both adenosine-5'-diphosphate (ADP, 5-50μM) and collagen (2-20μg/ml) induced concentration-related platelet aggregation in the microminipigs; 20μM ADP and 5 and 12.5μg/ml collagen were selected for further ex vivo studies. Aspirin plus prasugrel were administered orally for 7days (n=4/each group). Ex vivo platelet aggregation was analyzed on Day 1 (1 and 4h after administration), Day 4 (4h), and Day 7 (4h) under three different prasugrel dosing regimens: LD0/MD1 (1mg/kg/day), LD0/MD3 (3mg/kg/day), and LD10/MD1 (10mg/kg loading dose and 1mg/kg/day maintenance dose). Aspirin (10mg/kg/day) was administered to all groups. In the presence of aspirin, prasugrel at 3 and 10mg/kg significantly inhibited ADP-induced platelet aggregation on Day 1. On Days 4 and 7, significant inhibition of platelet aggregation (IPA) was also observed in each group. With 5μg/ml collagen-induced platelet aggregation, all three groups showed significant IPA at 4h on Day 1 or later. In 12.5μg/ml collagen-induced platelet aggregation, all groups showed significant effects on Days 4 and 7; however, the 30%-35% IPA was considerably lower than that (50%-60%) found with 5μg/ml collagen. In Clawn miniature pigs, similar inhibitory patterns were observed for both ADP- and collagen-induced ex vivo platelet aggregation. In conclusion, these results indicated that microminipigs as well as miniature pigs may represent useful experimental animals for thrombosis research.