贝叶斯方法在实验室研究向临床的转化以及辨识隐含亚群体中的应用

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (10): 1114-1121.

贝叶斯方法在实验室研究向临床的转化以及辨识隐含亚群体中的应用

出版日期:2007-10-26 发布日期:2020-11-04

Application of Bayesian Methods for laboratory to clinical translation and for identifying hidden subpopulations

David Z. D’ Argenio¹, WANG Xiao-ning², ZHOU Ze-xun²

¹Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA;
²Clinical Discovery, Strategic Modeling and Simulation Group, Bristol-Myers Squibb Co., Princeton, NJ 08543, USA

Online:2007-10-26 Published:2020-11-04
Contact: David Z.D' Argenio,Tel:213-740-0341 　E-mail:dargenio @bmsr.usc.edu

摘要/Abstract

摘要： 为研究药动学药效学而发展的建模方法遇有很多挑战, 部分原因是由于从实验室和临床试验得到的测量数据的数目和种类严重受限, 以及试验的波动和过程本身的不确定性。贝叶斯方法为PK/PD 建模及药物研发提供了一个框架, 可以解决上述一些问题。本文通过两个例子介绍了贝叶斯方法的实际应用:一是用群体建模方法, 研究抗逆转录病毒药物拉米夫定在感染HIV-1 青少年外周血单核细胞中的细胞动力学, 二是运用群体混合模型识别现有协变量所不能识别的隐藏亚群。

Abstract: Modeling methodologies developed for studying pharmacokinetic (PK)/pharmacodynamic (PD) processes confront many challenges related in part to the severe restrictions on the number and type of measurements that are available from laboratory experiments and clinical trials, as well as the variability in the experiments and the uncertainty associated with the processes themselves.Bayesian methods have provided a framework for PK/PD modeling and drug development that can address some of the above-mentioned challenges.This paper presents two illustrations of the application of Bayesian methods :the first involves a population modeling study of the cellular kinetics of the antiretroviral compound Lamivudine in the PBMCs of HIV-1 infected adolescents ;the second uses a population mixture modeling approach to identifying hidden subpopulations that can not be identified by available measured covariates.

Key words: antiretroviral drugs, lamivudine metabolism, population modeling, mixture models

. 贝叶斯方法在实验室研究向临床的转化以及辨识隐含亚群体中的应用[J]. 中国临床药理学与治疗学, 2007, 12(10): 1114-1121.

David Z. D’ Argenio, WANG Xiao-ning, ZHOU Ze-xun. Application of Bayesian Methods for laboratory to clinical translation and for identifying hidden subpopulations[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(10): 1114-1121.

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