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.
ABSTRACT
The China Food and Drug Administration (CFDA) modulated the Drug Registration Regulation at 2016.In this article,the registration classification of chemical drug was analyzed,and the definition,cormotation and technical standard of new drugs and generic drugs were compared.Compared with the 2007 version of regulations,obvious changes have happened,the scope of new drugs has been narrowed,and the definition is more strict and accurate,the scope of generic drugs has been expanded.The new regulation keeps the same evaluation standards with the ICH,FDA and EMA.Regulatory changes have a profound impact on the medical research and development:promoting the reformulation of domestic pharmaceutical market,encouraging R&D and innovation in enterprises and accelerating the pace towards the international market.