目的 考察阿哌沙班大鼠體內(nèi)藥動(dòng)學(xué)并評(píng)價(jià)其與藥效學(xué)的相關(guān)性。方法 采用超高效液相色譜-串聯(lián)質(zhì)譜（UPLC-MS/MS）測(cè)定不同時(shí)間阿哌沙班血藥濃度并繪制血藥濃度-時(shí)間曲線，同時(shí)測(cè)定各時(shí)間點(diǎn)凝血酶原時(shí)間（PT）延長(zhǎng)倍數(shù)并繪制藥效-時(shí)間曲線，對(duì)藥動(dòng)及藥效進(jìn)行相關(guān)性分析。結(jié)果 阿哌沙班以2 mg/kg劑量iv給予大鼠，血藥濃度時(shí)間曲線下面積（AUC_0-∞）、半衰期（t_1/2z）分別為（4 016.07±1 160.46）μg·h/L、（2.95±1.59）h；以10 mg/kg劑量ig給藥，AUC_0-∞、t_1/2z、峰濃度（C_max）、達(dá)峰時(shí)間（t_max）、生物利用度（F）分別為（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劑量ig給藥后0.5~2.0 h可顯著延長(zhǎng)PT，以各時(shí)間點(diǎn)PT延長(zhǎng)倍數(shù)對(duì)血藥濃度作圖呈良好的線性關(guān)系。結(jié)論 阿哌沙班大鼠ig給藥F高，吸收迅速，延長(zhǎng)PT的效應(yīng)與血藥濃度呈現(xiàn)良好的相關(guān)性。

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 AUC_0-∞ and T_1/2z 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 AUC_0-∞, T_1/2z, C_max, T_max 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.