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A population PK/PD Analysis for CPRC2,a Potent Factor Xa Inhibitor,in Healhty Chinese Subjects

Yang LiuDongyang LiuXia ChenHanlin SongYiwen WuQian ZhaoPei HuJi Jiang

Phase I Unit,Clinical Pharmacology Research Center,Peking Union Medical College Hospital and Chinese Academy of Medical Sciences

摘要:<正>As a new class of drugs to prevent venous thromboembolism,Factor Xa inhibitor showed wider safety window than warfarin.CPRC2,a new oral specific Factor Xa inhibitor,is currently under clinical development.A Phase I clinical trial including single dose study and multiple dose study has been conducted in 24 healthy Chinese subjects aged from 21-44 years old in our Unit.Blood and urine were sampled according to scheduled time.To receive PK profiles,parent drug(CPRC2) and its active metabolite(CPRC2M) were determined in both of plasma and urine.At the same time,activity of antiFXa, activated partial thromboplastin time(APTT),and prothrombintime(PT) were also detected as pharmacodynamics response.Following by a non-compartmental analysis,a population PK/PD model was developed to mimic PK/PD profiles simultaneously for single and multiple dose studies to support future clinical development.NONMEM(V7.1) interfaced with PsN was used to conduct population PK/PD analysis.A simple two compartment PK model with first-order absorption and linear elimination was proposed with mixed error model as residual error model.Because of neglectable time delay between PK and PD profiles,anEmax model was used to indicate the effects of drug concentrations on activity of antiFXa,which was further used to predict PT and APTT using linear model.This base PK/PD model was then used to test the effects of various covariates.The proposed final PK/PD model quantitatively determined the effects of covariates on CPRC2 PK/PD profiles and mimicked it well.It was validated by VPC method.This proposed Pop-PK/PD model was hopefully to support further clinical development of CPRC2.
会议名称:

第四届定量药理学与新药评价国际会议·2013

会议时间:

2013-11-01

会议地点:

中国北京

  • 专辑:

    医药卫生科技

  • 专题:

    药学

  • 分类号:

    R96

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