Skip to Main content Skip to Navigation
Journal articles

Pharmacokinetic-pharmacodynamic models for categorical toxicity data

Abstract : We propose a pharmacokinetic-pharmacodynamic (PK/PD) model (with possibly different choices for the PD link) for categorical toxicity data analysis. This is extension of the one-comportment model that applies to toxic endpoints categorised by grades (e.g., benign, mild, severe, and very severe). The model assumes that the area under the curve (AUC) of the internal quantity of the chemical substance is the critical dose-metric that drives the acute toxic phenomenon. That model handles time-varying concentrations and takes into account follow-up time, i.e., time at which effects are observed. Moreover the model bridges mechanistically based dose-response models and standard dose-response models, retaining the advantages of both. We use Markov chain-Monte Carlo (MCMC) simulations to fit the model to mortality data for mice exposed to chlorine, rats exposed to ammonia, and categorical data (different severity levels) from acute exposures of rats and humans to hydrogen sulfide.
Document type :
Journal articles
Complete list of metadata
Contributor : Gestionnaire Civs Connect in order to contact the contributor
Submitted on : Friday, March 21, 2014 - 2:05:55 PM
Last modification on : Friday, March 21, 2014 - 2:05:57 PM

Links full text




Cheikh Diack, Frédéric Y. Bois. Pharmacokinetic-pharmacodynamic models for categorical toxicity data. Regulatory Toxicology and Pharmacology, Elsevier, 2005, 41 (1), pp.55-65. ⟨10.1016/j.yrtph.2004.09.007⟩. ⟨ineris-00962936⟩



Record views