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[摘要]
目的 考察阿哌沙班大鼠体内药动学并评价其与药效学的相关性。方法 采用超高效液相色谱-串联质谱(UPLC-MS/MS)测定不同时间阿哌沙班血药浓度并绘制血药浓度-时间曲线,同时测定各时间点凝血酶原时间(PT)延长倍数并绘制药效-时间曲线,对药动及药效进行相关性分析。结果 阿哌沙班以2 mg/kg剂量iv给予大鼠,血药浓度时间曲线下面积(AUC0-∞)、半衰期(t1/2z)分别为(4 016.07±1 160.46)μg·h/L、(2.95±1.59)h;以10 mg/kg剂量ig给药,AUC0-∞、t1/2z、峰浓度(Cmax)、达峰时间(tmax)、生物利用度(F)分别为(17 973.48±3 145.30)μg·h/L、(1.52±0.36)h、(4 949.12±615.38)μg/L、(1.00±0.71)h、89.5%。阿哌沙班以10 mg/kg剂量ig给药后0.5~2.0 h可显著延长PT,以各时间点PT延长倍数对血药浓度作图呈良好的线性关系。结论 阿哌沙班大鼠ig给药F高,吸收迅速,延长PT的效应与血药浓度呈现良好的相关性。
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[Abstract]
Objective To study pharmacodynemics and pharmacokenitics of apixaban in rats and investigate the correlation between them. Mehtods The UPLC-MS/MS method was applied to determining the plasma concentration of apixaban and draw the concentration-time curve. Meanwhile, the extension rate of prothrombin time (PT) was determined to draw the effect-time curve. Then the relationship between concentration and effect could be evaluated. Results After iv administration of apixaban (2 mg/kg) in rats, the main pharmacokinetic parameters AUC0-∞ and T1/2z were (4 016.07 ±1 160.46) μg·h/L and (2.95 ±1.59) h, respectively. After ig administration of apixaban (10 mg/kg), the main pharmacokinetic parameters AUC0-∞, T1/2z, Cmax, Tmax and bioavailability were (17 973.48 ±3145.30) μg·h/L, (1.52 ±0.36) h, (4 949.12 ±615.38) μg/L, (1.00 ±0.71) h and 89.5%, respectively. Apixaban (10 mg/kg) significantly increased PT and the effect lasted about 2 h. The changes of apixaban plasma concentration and PT extension rate were synchronous. Conclusion Apixaban has the characteristics of high oral bioavailability and rapid absorption. There is a significant correlation between PT extension rate and its plasma concentration after ig administration of 10 mg/kg in rats.
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