Development of physiologically based pharmacokinetic and physiologically based pharmacodynamic models for applications in toxicology and risk assessment.
1993 Decision support methodologies international workshop. Atlanta GA USA, 1993/10/18.
Pharmacokinetics (PK) involves the study of the rates of absorption, distribution, excretion, and biotransformation of chemicals and their metabolites.
PK models can be used to reconstruct extensive time-course data sets based on a small number of kinetic parameters.
These models can be used to predict the results of new experiments and integrate studies on kinetics, disposition and metabolism in various animal species . The 2 main approaches that have been pursued in developing PK models are : (1) data-based compartmental modeling ; and (2) physiologically based compartmental modeling.
Data-based models rely on the collection of time-course concentration data and fitting these data with mathematical models.
Compartments in these models do not necessarily reflect the anatomy and physiology of the animal, and the kinetic constants derived from these models do not have obvious physiological or biochemical counterparts.
In physiologically based pharmacokinetic (PBPK) models, compartments correspond more closely to actual anatomical structures, defined with respect to their volumes, blood flows, chemical binding characteristics, and ability to metabolize or excrete the compounds of interest.
Because the kinetic parameters of these models reflect tissue blood flows, partitioning, and biochemical constants, these models are more readily scaled from one animal species to another.
Mots-clés Pascal : Toxicologie, Evaluation, Risque, Modèle PBPK, Toxicité, Homme, Extrapolation animal homme, Modèle PBPD
Mots-clés Pascal anglais : Toxicology, Evaluation, Risk, PBPK modeling, Toxicity, Human, Man animal extrapolation
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 95-0525724
Code Inist : 002B03A. Création : 01/03/1996.