Pharmacokinetic-pharmacodynamic study of apixaban in rats / 药物评价研究

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.