Effect of clopidogrel on thrombin generation in platelet-rich plasma in the rat.
Clopidogrel (25 mg/kg, p.o.), a potent and selective inhibitor of ADP-induced platelet aggregation, significantly inhibited, in the presence of platelets, ex vivo thrombin generation triggered by low concentrations of tissue factor. Clopidogrel reduced the area under the curve (23%, p <0.05) and the thrombin peak concentration (35%, p <0.05) but did not affect the lag phase of thrombin generation. Under the same experimental conditions, heparin (100 microg/ml) inhibited thrombin generation mostly by delaying and by reducing the burst of thrombin. In a stasis-induced venous thrombosis model in rats under low thrombogenic challenge, clopidogrel inhibited thrombus formation (ED50 = 7.9+/-1.5 mg/kg, p.o. - n = 10), confirming the existence of a close relationship between platelet activation and thrombin generation leading to blood coagulation and venous thrombosis.
Hérault
J P
JP
Haemobiology Research Department, Sanofi Recherche, Toulouse, France.
Dol
F
F
Gaich
C
C
Bernat
A
A
Herbert
J M
JM
D000818:Animals; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology; D000077144:Clopidogrel; D005434:Flow Cytometry; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000096:biosynthesis*; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013917:Thrombin; D013988:Ticlopidine