An approximate method for population toxicokinetic analysis with aggregated data

Weihsueh A. Chiu (1) , Frédéric Y. Bois (2)

1 National Center for Environmental Assessment
2 INERIS - Institut National de l'Environnement Industriel et des Risques

Standard statistical models for analyzing inter-individual variability in clinical pharmacokinetics (nonlinear mixed effects; hierarchical Bayesian) require individual data. However, for environmental or occupational toxicants only aggregated data are usually available, so toxicokinetic analyses typically ignore population variability. We propose a hierarchical Bayesian approach to estimate inter-individual variability from the observed mean and variance at each time point, using a bivariate normal (or lognormal) approximation to their joint likelihood. Through analysis of both simulated data and real toxicokinetic data from 1,3-butadiene exposures, we conclude that given information on the form of the individual-level model, useful information on inter-individual variability may be obtainable from aggregated data, but that additional sensitivity and identifiability checks are recommended.

Keywords: MODELES HIERARCHIQUES; ANALYSE BAYESIENNE; DONNEES MANQUANTES; INFERENCE STATISTIQUE; METHODE DES MOMENTS<br />---<br />1-3 BUTADIENE; BAYESIAN; INTER-INDIVIDUAL VARIABILITY; MARKOV CHAIN MONTE CARLO SIMULATION; POPULATION PHARMACOKINETICS

Domains: Environmental Sciences

Weihsueh A. Chiu, Frédéric Y. Bois. An approximate method for population toxicokinetic analysis with aggregated data. Journal of Agricultural Biological and Environmental Statistics, 2007, 12 (3), pp.346-363. ⟨10.1198/108571107X229340⟩. ⟨ineris-00961914⟩