Pharmacokinetic/pharmacodynamic modeling in drug development

被引:219
作者
Sheiner, LB [1 ]
Steimer, JL
机构
[1] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[4] F Hoffmann La Roche & Co Ltd, Pharmaceut Dev Biostat, CH-4070 Basel, Switzerland
关键词
mechanistic models; learning; confirming; empirical models; predictive models; statistical modeling;
D O I
10.1146/annurev.pharmtox.40.1.67
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We propose a framework for considering the role of pharmacokinetic/pharmacodynamic modeling in drug development and an appraisal of its current and potential impact on that activity. After some introduction, definitions, and background information on drug development, we discuss subject-matter models that underlie pharmacokinetic/pharmacodynamic modeling and show how they determine appropriate statistical models. We discuss the broad role modeling can play in drug development, enhancing primarily the "learning" steps, i.e. acquiring the information needed for the label and for planning efficient confirmatory clinical trials. Examples of past applications of modeling to drug development are presented in tabular form, followed by a discussion of some practical issues in application. Modeling will not reach its potential utility until it is manifest as a visible and separate work unit within a drug development program. We suggest that that work unit is the "in numero" study: a protocol-driven exercise designed to extract additional information, and/or answer a specific drug-development question, through an integrated model-based (meta-) analysis of existent raw data, often pooled across separate (clinical) studies.
引用
收藏
页码:67 / 95
页数:29
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