title: Characterization of platelet aggregation responses in microminipigs: Comparison with miniature pigs and the influence of dual antiplatelet administration of aspirin plus prasugrel.
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 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.
authors.affiliation: Biological Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohno
authors.affiliation: Biological Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Tomizawa
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jakubowski
authors.affiliation: Biological Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Biological Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan. Electronic address: sugidachi.atsuhiro.r7@daiichisankyo.co.jp.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Sugidachi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D004359:Drug Therapy, Combination; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D010975:Platelet Aggregation Inhibitors; D000068799:Prasugrel Hydrochloride; D001241:Aspirin
keywords: Antiplatelet; Aspirin; Microminipig; Miniature Pig; Platelet Aggregation; Prasugrel