阿哌沙班在大鼠体内药动学/药效学研究  

Pharmacokinetic-pharmacodynamic study of apixaban in rats

作　　者：任利翔[1] 王婉秋[2] 林鹤[1] 光海红[2] 邢立国[1] 

机构地区：[1]沈阳化工研究院有限公司安评中心,辽宁沈阳110021 [2]沈阳化工研究院有限公司医药研究室,辽宁沈阳110021

出　　处：《药物评价研究》2017年第9期1290-1293,共4页Drug Evaluation Research

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(AUC_(0-∞))、半衰期(t_(1/2z))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,AUC_(0-∞)、t_(1/2z)、峰浓度(C_(max))、达峰时间(t_(max))、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。Objective To study pharmacodynemics and pharmacokenitics ofapixaban in rats and investigate the correlation betweenthem. Mehtods The UPLC-MS/MS method was applied to determining the plasma concentration of apixaban and draw theconcentration-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 Tl/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, Tl/2z, Cmax, Tmax and bioavailabilitywere （17 973.48 ± 3145.30） μg·h/L, （1.52 ± 0.36） h, （4 949.12 ± 615.38） μg·h/L, （1.00 ± 0.71） h and 89.5%, respectively. Apixaban （10mg/kg） significantly increased PT and the effect lasted about 2 h. The changes of apixaban plasma concentration and PT extensionrate were synchronous. Conclusion Apixaban has the characteristics of high oral bioavailability and rapid absorption. There is asignificant correlation between PT extension rate and its plasma concentration after ig administration of 10 mg/kg in rats.

关 键 词：阿哌沙班 药动学 药效学 凝血酶原时间 

分 类 号：R965.2[医药卫生—药理学]