|
|
 |
 |
| |
 Printable version |
Physiological modelling of metabolic interactions |
Environnement, Risques & Santé. Volume 8, Number 5, 413-24, septembre-octobre 2009, Article original
|
 Résumé
Texte intégral
|
Author(s) : Frédéric Yves Bois |
Summary : Modeling metabolic interactions between chemicals can be a task of formidable complexity. Here I present a new approach and new tools to facilitate that development. GNU MCSim software is used to automatically merge individual models of metabolic pathways and couple them to a physiologically-based pharmacokinetic (PBPK) model. The global model thus generated can simulate interactions between a theoretically unlimited number of substances. Development time increases only linearly with the number of substances considered, while the number of possible interactions increases exponentially. This approach is applied to a simulated metabolic network involving an arbitrary mixture of 30 chemicals. The qualitative and quantitative behavior of the corresponding pathway network is analyzed with Monte Carlo simulations. In our example, the number of significant interactions, given the uncertainty and variability affecting the pharmacokinetics and metabolism of those substances, is much lower than the number of interactions theoretically possible. |
Keywords : Computer models, complex mixtures, drug interactions, food-drug interactions, metabolism, pharmacokinetics, systems biology, toxic actions |
|
