Statistical methods for population pharmacokinetic modelling

A principal aim of population pharmacokinetic studies is to estimate the variance components associated with intra- and inter-individual variability in observed drug concentrations. The explanation of the inter-individual variability in terms of subject-specific covariates is also of great importance. Pharmacokinetic models are nonlinear in the parameters and estimation is not straightforward. Within this paper we review a number of estimation approaches which have been suggested for population pharmacokinetic analyses. We distinguish between Bayesian and non-Bayesian and fully-parametric, semi-parametric and nonparametric methods.