Inhibition of factor Xa-induced platelet aggregation by a selective thrombin inhibitor, argatroban.
In the present study, a direct selective thrombin inhibitor, argatroban, and an indirect non-selective inhibitor, heparin, were examined for the inhibitory effect on factor Xa-induced platelet aggregation. Platelet aggregation was induced by thrombin or factor Xa+prothrombin in the presence of Ca++ using rabbit gel-filtered platelets. IC50 of argatroban on factor Xa-induced aggregation was 5-7 times higher than that on thrombin-induced aggregation, while IC50 of heparin in the presence of antithrombin III on factor Xa-induced aggregation was 90-200 times higher than that on thrombin-induced aggregation. This finding suggests that argatroban inhibits thrombin generating on the platelet surface more efficiently than heparin, and this may be one of the reasons for the higher efficacy of argatroban in arterial thrombosis as compared with heparin.
Kawai
H
H
Pharmaceuticals Laboratory, Mitsubishi Kasei Corporation, Yokohama, Japan.
Yamamoto
T
T
Hara
H
H
Tamao
Y
Y
D000818:Animals; D000991:Antithrombins / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D065427:Factor Xa Inhibitors; D010875:Pipecolic Acids / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013449:Sulfonamides
D000991:Antithrombins; D065427:Factor Xa Inhibitors; D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban