PBPK modelling of inter-individual variability in the pharmacokinetics of environmental chemicals

被引：124

作者：

Bois, Frederic Y. ^{[1
,2
]}

Jamei, Masoud ^{[3
]}

Clewell, Harvey. J. ^{[4
]}

机构：

[1] INERIS, F-60550 Verneuil En Halatte, France

[2] Univ Technol Compiegne, Chair Math Modelling Syst Toxicol, Royallieu Res Ctr, UTC, F-60205 Compiegne, France

[3] Simcyp Ltd, Blades Enterprise Ctr, Sheffield S2 4SU, S Yorkshire, England

[4] Hamner Inst Hlth Sci, Res Triangle Pk, NC 27709 USA

来源：

TOXICOLOGY | 2010年 / 278卷 / 03期

关键词：

Drug-drug interactions; Monte Carlo simulations; PBPK models; Population models; Susceptible populations; Toxicokinetics; PLASMA PARTITION-COEFFICIENTS; MAXIMUM-LIKELIHOOD-ESTIMATION; ORGANIC CATION TRANSPORTERS; INTRINSIC CLEARANCE DATA; IN-VITRO DATA; RISK-ASSESSMENT; DRUG CLEARANCE; CANCER-RISK; P-GLYCOPROTEIN; POPULATION PHARMACOKINETICS;

D O I：

10.1016/j.tox.2010.06.007

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Generic PBPK models, applicable to a large number of substances, coupled to parameter databases and QSAR modules, are now available for predictive modelling of inter-individual variability in the absorption, distribution, metabolism and excretion of environmental chemicals. When needed, Markov chain Monte Carlo methods and multilevel population models can be jointly used for a Bayesian calibration of a PBPK model, to improve our understanding of the determinants of population heterogeneity and differential susceptibility. This article reviews those developments and illustrates them with recent applications to environmentally relevant questions. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

引用

页码：256 / 267

页数：12

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