Document Detail


A stochastic whole-body physiologically based pharmacokinetic model to assess the impact of inter-individual variability on tissue dosimetry over the human lifespan.
MedLine Citation:
PMID:  20122977     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Physiologically based pharmacokinetic (PBPK) models have proven to be successful in integrating and evaluating the influence of age- or gender-dependent changes with respect to the pharmacokinetics of xenobiotics throughout entire lifetimes. Nevertheless, for an effective application of toxicokinetic modelling to chemical risk assessment, a PBPK model has to be detailed enough to include all the multiple tissues that could be targeted by the various xenobiotics present in the environment. For this reason, we developed a PBPK model based on a detailed compartmentalization of the human body and parameterized with new relationships describing the time evolution of physiological and anatomical parameters. To take into account the impact of human variability on the predicted toxicokinetics, we defined probability distributions for key parameters related to the xenobiotics absorption, distribution, metabolism and excretion. The model predictability was evaluated by a direct comparison between computational predictions and experimental data for the internal concentrations of two chemicals (1,3-butadiene and 2,3,7,8-tetrachlorodibenzo-p-dioxin). A good agreement between predictions and observed data was achieved for different scenarios of exposure (e.g., acute or chronic exposure and different populations). Our results support that the general stochastic PBPK model can be a valuable computational support in the area of chemical risk analysis.
Authors:
Rémy Beaudouin; Sandrine Micallef; Céline Brochot
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-01
Journal Detail:
Title:  Regulatory toxicology and pharmacology : RTP     Volume:  57     ISSN:  1096-0295     ISO Abbreviation:  Regul. Toxicol. Pharmacol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-04-21     Completed Date:  2010-07-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8214983     Medline TA:  Regul Toxicol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  103-16     Citation Subset:  IM    
Copyright Information:
(c)2010 Elsevier Inc. All rights reserved.
Affiliation:
INERIS, Institut National de l'Environnement Industriel et des Risques, Unité Modèles pour l'Ecotoxicologie et la Toxicologie (METO), Parc ALATA, BP2, 60550 Verneuil en Halatte, France. Remy.Beaudouin@ineris.fr
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MeSH Terms
Descriptor/Qualifier:
Aging / metabolism*,  physiology
Body Burden
Body Weight / physiology
Butadienes / pharmacokinetics
Dose-Response Relationship, Drug
Female
Humans
Male
Models, Biological*
Organ Size / physiology
Physiological Phenomena*
Stochastic Processes
Tetrachlorodibenzodioxin / pharmacokinetics
Time Factors
Tissue Distribution / physiology
Xenobiotics / pharmacokinetics*
Chemical
Reg. No./Substance:
0/Butadienes; 0/Xenobiotics; 106-99-0/1,3-butadiene; 1746-01-6/Tetrachlorodibenzodioxin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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