通过贝叶斯- pbpk模型评估个体间变异性

Q3 Pharmacology, Toxicology and Pharmaceutics

Drug Discovery Today: Disease Models Pub Date : 2016-12-01 DOI:10.1016/j.ddmod.2017.08.001

Markus Krauss, Andreas Schuppert

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引用次数: 3

摘要

个体间变异性的描述以及这种变异性的ADME相关来源(ADME:吸收、分布、代谢、排泄)是临床药物开发中识别无反应或高危患者的潜在相关亚组的基本要素。基于生理的药代动力学(PBPK)模型的使用支持对与药物药代动力学相关的潜在ADME过程的机制理解。此外，将贝叶斯统计整合到PBPK应用中，可以彻底评估药物的个体间变异性和药代动力学行为的不确定性以及潜在的模型参数。贝叶斯- pbpk方法的最新应用包括亚组分层或改善药代动力学外推的稳健性。

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Assessing interindividual variability by Bayesian-PBPK modeling

The description of interindividual variability and the ADME-related sources of such variability (ADME: absorption, distribution, metabolization, excretion) is an essential element in clinical drug development to identify potentially relevant subgroups of non-responders or high-risk patients. The use of physiologically-based pharmacokinetic (PBPK) models supports a mechanistic understanding of the underlying ADME processes related to drug pharmacokinetics. In addition, the integration of Bayesian statistics into PBPK applications has allowed thorough assessment of interindividual variability and uncertainty of the pharmacokinetic behavior of drugs and underlying model parameters. Recent applications of Bayesian-PBPK approaches include subgroup stratification or improvement of the robustness of pharmacokinetic extrapolations.

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来源期刊

Drug Discovery Today: Disease Models Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

自引率

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期刊介绍： Drug Discovery Today: Disease Models discusses the non-human experimental models through which inference is drawn regarding the molecular aetiology and pathogenesis of human disease. It provides critical analysis and evaluation of which models can genuinely inform the research community about the direct process of human disease, those which may have value in basic toxicology, and those which are simply designed for effective expression and raw characterisation.