{"title":"Assessing interindividual variability by Bayesian-PBPK modeling","authors":"Markus Krauss, Andreas Schuppert","doi":"10.1016/j.ddmod.2017.08.001","DOIUrl":null,"url":null,"abstract":"<div><p>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<span> 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.</span></p></div>","PeriodicalId":39774,"journal":{"name":"Drug Discovery Today: Disease Models","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmod.2017.08.001","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Discovery Today: Disease Models","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1740675717300373","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 3
Abstract
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.
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.
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