各種血小板凝集抑制薬の健常人における臨床試験

Abstract

The platelet aggregation inhibitory activity of antithrombotic agents, dipyridamole, limaprost (α-cyclodextrin clathrate), cilostazol, and ticlopidine was tested on ten healthy human volunteers.Dipyridamole (at the dose of 300 mg/day), limaplost (30 μg/day), cilostazol (200 mg/day), and ticlopidine (300 mg/day) were orally administrated for 7 days. The post-drug platelet aggregation was compared with pre-drug control to determine antiplatelet activity of each drug. The concentrations of β-thromboglobulin (β-TG) and platelet factor 4 (PF-4) were also determined to evaluate drug effect on the blood coagulation system.Platelet aggregation was induced by ADP, collagen, epinephrine, and arachidonic acid. To obtain the optimal concentration and personal baseline, blood platelet aggregation response by the 4 inducers on each volunteer were predetermined. Plasma samples were prepared to uniformly contain platelets at a concentration of 3 × 105/μl.In a comparison of the area under the aggregation response curve during an early phase of testing, dipiridamole and limaprost did not exhibit the antiplatelet effect against any of the 4 inducers. In contrast, cilostazol inhibited significantly the aggregation due to ADP (P<0.05), and arachidonic acid (P<0.01), and ticlopidine also inhibited the aggregation by ADP (P<0.01), collagen (P<0.01), and epinephrine (P<0.05). Similar results were obtained by a comparison of the maximum aggregation rates.β-TG and PF-4 concentrations did not indicate any specific changes in their time profiles.