Characterization of platelet aggregation responses in microminipigs: Comparison with miniature pigs and the influence of dual antiplatelet administration of aspirin plus prasugrel

Thrombosis Research
Kousaku OhnoAtsuhiro Sugidachi

Abstract

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 co...Continue Reading

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Citations

Jun 16, 2016·Toxicologic Pathology·Akihisa KangawaMasatoshi Shibata
Oct 10, 2018·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Kazuichi Nakamura, Masayoshi Otake

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