IR@PKUHSC  > 北京大学第一临床医学院  > 药剂科
学科主题临床医学
Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers
Zhang, Dong-mei2; Wang, Kun1; Zhao, Xia2; Li, Yun-fei1; Zheng, Qing-shan1; Wang, Zi-ning2; Cui, Yi-min2
关键词Anticoagulation Therapy Bivalirudin Activated Clotting Time Healthy Young Chinese Subjects Population Pharmacokinetics And Pharmacodynamics
刊名ACTA PHARMACOLOGICA SINICA
2012-11-01
DOI10.1038/aps.2012.37
33期:11页:1387-1394
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]PERCUTANEOUS CORONARY INTERVENTION ; CARDIOPULMONARY BYPASS ; PHARMACOLOGY ; HEPARIN
英文摘要

Aim: To investigate the population pharmacokinetics (PK) and pharmacodynamics (PD) of bivalirudin, a synthetic bivalent direct thrombin inhibitor, in young healthy Chinese subjects.

Methods: Thirty-six young healthy volunteers were randomly assigned into 4 groups received bivalirudin 0.5 mg/kg, 0.75 mg/kg, and 1.05 mg/kg intravenous bolus, 0.75 mg/kg intravenous bolus followed by 1.75 mg/kg intravenous infusion per hour for 4 h. Blood samples were collected to measure bivalirudin plasma concentration and activated clotting time (ACT). Population PK-PD analysis was performed using the nonlinear mixed-effects model software NONMEM. The final models were validated with bootstrap and prediction-corrected visual predictive check (pcVPC) approaches.

Results: The final PK model was a two-compartment model without covariates. The typical PK population values of clearance (CL), apparent distribution volume of the central-compartment (V-1), inter-compartmental clearance (Q) and apparent distribution volume of the peripheral compartment (V-2) were 0.323 L.h(-1).kg(-1), 0.086 L/kg, 0.0957 L.h(-1).kg(-1), and 0.0554 L/kg, respectively. The inter-individual variabilities of these parameters were 14.8%, 24.2%, fixed to 0% and 15.6%, respectively. The final PK-PD model was a sigmoid E-max model without the Hill coefficient. In this model, a covariate, red blood cell count (RBC star), had a significant effect on the EC50 value. The typical PD population values of maximum effect (E-max), EC50, baseline ACT value (E-0) and the coefficient of RBC star on EC50 were 318 s, 2.44 mg/L, 134 s and 1.70, respectively. The inter-individual variabilities of E-max, EC50, and E-0 were 6.80%, 46.4%, and 4.10%, respectively.

Conclusion: Population PK-PD models of bivalirudin in healthy young Chinese subjects have been developed, which may provide a reference for future use of bivalirudin in China.

语种英语
WOS记录号WOS:000310778400008
资助机构Shenzhen Main Luck pharmaceuticals, Inc.
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50828
专题北京大学第一临床医学院_药剂科
作者单位1.Peking Univ, Hosp 1, Dept Pharm, Beijing 100034, Peoples R China
2.Shanghai Univ Tradit Chinese Med, Ctr Drug Clin Res, Lab Pharmacometr, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Dong-mei,Wang, Kun,Zhao, Xia,et al. Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers[J]. ACTA PHARMACOLOGICA SINICA,2012,33(11):1387-1394.
APA Zhang, Dong-mei.,Wang, Kun.,Zhao, Xia.,Li, Yun-fei.,Zheng, Qing-shan.,...&Cui, Yi-min.(2012).Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers.ACTA PHARMACOLOGICA SINICA,33(11),1387-1394.
MLA Zhang, Dong-mei,et al."Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers".ACTA PHARMACOLOGICA SINICA 33.11(2012):1387-1394.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Zhang, Dong-mei]的文章
[Wang, Kun]的文章
[Zhao, Xia]的文章
百度学术
百度学术中相似的文章
[Zhang, Dong-mei]的文章
[Wang, Kun]的文章
[Zhao, Xia]的文章
必应学术
必应学术中相似的文章
[Zhang, Dong-mei]的文章
[Wang, Kun]的文章
[Zhao, Xia]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。