生物活性

• 描述Factor Xa (FXa) is a coagulation factor thrombokinase responsible for the generation of thrombin. Edoxaban is a direct, selective FXa inhibitor with a K_i value of 0.561nM. In uman plasma samples, the minimum concentrations of edoxaban needed to significantly prolong prothrombin time (PT) and activated partial thromboplastin time were 55 and 50ng/mL, respectively. Plasma edoxaban at the concentration of 5.5 – 1640 ng/ml inhibited the generation of thrombin in a dose-dependent manner. Edoxaban above 10 ng/ml significantly extended the initiation phase of thrombin generation. In human platelet-poor plasma, the peak IC50 value, mRate IC50 value, and endogenous thrombin potential (ETP) IC50 value measured in thrombin generation assay were 0.145, 0.047, and 1.39 µM, respectively. The doses of edoxaban required to reach 50% of inhibition of CT2 lag time and ttPeak were 0.188 and 0.139 µM, respectively. In human platelet-rich plasma, the peak IC50, mRate IC50, and ETP IC50 values were 0.305, 0.230, and 0.636 µM, respectively. In apolipoprotein E (ApoE)-deficient mice, the treatment with 15 mg/kg edoxaban one hour before vascular injury almost completely prevented thrombus formation, and significantly decreased the time to occlusion and the patency rate. The following chronic oral administration of 10 mg/kg edoxaban by gavage b.i.d for six weeks significantly suppressed neointimal hyperplasia.
• 作用机制Edoxaban inhibits free FXa by directly binding to FXa without the need of antithrombin, thereby preventing the conversion of prothrombin to thrombin.

• 动物研究
  剂量	Rat: 0.3 mg/kg - 3 mg/kg[3] (p.o.)
  给药途径	p.o.
  动物药代数据	Animal Rats[4] Dose 1 mg/kg Administration p.o. or i.v. AUC0→24h 212 ± 87 ng·h/ml (p.o.) 545 ± 21 ng·h/ml (i.v.) AUC0-inf 301 ng·h/ml (p.o.) 539 ± 29 ng·h/ml (i.v.) T1/2 4.85 ± 2.88 h (p.o.) 1.32 ± 0.69 h (i.v.) Tmax 0.500 ± 0.000 h (p.o.) AUClast 184 ± 94 ng·h/ml (p.o.) 516 ± 29 ng·h/ml (i.v.) CL 1.86 ± 0.10 L/h/kg (i.v.) Cmax 72.7 ± 35.7 ng/ml (p.o.) Vss 2.14 ± 0.36 L/kg (i.v.)