Hérault J P, Dol F, Gaich C, Bernat A, Herbert J M
Haemobiology Research Department, Sanofi Recherche, Toulouse, France.
Thromb Haemost. 1999 Jun;81(6):957-60.
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.
氯吡格雷（25毫克/千克，口服）是一种强效且选择性的ADP诱导血小板聚集抑制剂，在有血小板存在的情况下，它能显著抑制低浓度组织因子引发的体外凝血酶生成。氯吡格雷降低了曲线下面积（23%，p<0.05）和凝血酶峰值浓度（35%，p<0.05），但不影响凝血酶生成的延迟期。在相同实验条件下，肝素（100微克/毫升）主要通过延迟和减少凝血酶的爆发来抑制凝血酶生成。在低血栓形成挑战下的大鼠静脉淤滞诱导血栓形成模型中，氯吡格雷抑制血栓形成（半数有效剂量=7.9±1.5毫克/千克，口服 - n = 10），证实了血小板活化与导致血液凝固和静脉血栓形成的凝血酶生成之间存在密切关系。
