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

• Published in: Thrombosis research Vol. 135; no. 5; pp. 933 - 938
• Main Authors: Ohno, Kousaku, Tomizawa, Atsuyuki, Jakubowski, Joseph A, Mizuno, Makoto, Sugidachi, Atsuhiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.05.2015
• Subjects: Administration, Oral; Animals; Antiplatelet; Aspirin; Aspirin - administration & dosage; Aspirin - therapeutic use; Blood Platelets - cytology; Blood Platelets - drug effects; Drug Therapy, Combination; Hematology, Oncology and Palliative Medicine; Male; Microminipig; Miniature Pig; Platelet Aggregation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - therapeutic use; Platelet Function Tests; Prasugrel; Prasugrel Hydrochloride - administration & dosage; Prasugrel Hydrochloride - therapeutic use; Swine; Swine, Miniature; Platelet Aggregation; Prasugrel; Microminipig; Antiplatelet; Aspirin; Miniature Pig
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2015.02.014

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, 5–50 μM) and collagen (2–20 μg/ml) induced concentration-related platelet aggregation in the microminipigs; 20 μM ADP and 5 and 12.5 μg/ml collagen were selected for further ex vivo studies. Aspirin plus prasugrel were administered orally for 7 days (n = 4/each group). Ex vivo platelet aggregation was analyzed on Day 1 (1 and 4 h after administration), Day 4 (4 h), and Day 7 (4 h) under three different prasugrel dosing regimens: LD0/MD1 (1 mg/kg/day), LD0/MD3 (3 mg/kg/day), and LD10/MD1 (10 mg/kg loading dose and 1 mg/kg/day maintenance dose). Aspirin (10 mg/kg/day) was administered to all groups. In the presence of aspirin, prasugrel at 3 and 10 mg/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 5 μg/ml collagen-induced platelet aggregation, all three groups showed significant IPA at 4 h on Day 1 or later. In 12.5 μg/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 5 μg/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.