Estimation of population pharmacokinetics using the Gibbs sampler

Quantification of the average and interindividual variation in pharmacokinetic behavior within the patient population is an important aspect of drug development. Population pharmacokinetic models typically involve large numbers of parameters related nonlinearly to sparse, observational data, which creates difficulties for conventional methods of analysis. The nonlinear mixed-effects method implemented in the computer program NONMEM is a widely used approach to the estimation of population parameters. However, the method relies on somewhat restrictive modeling assumptions to enable efficient parameter estimation. In this paper we describe a Bayesian approach to population pharmacokinetic analysis which used a technique known as gibbs sampling to simulate values for each model parameter. We provide details of how to implement the method in the context of population pharmacokinetic analysis, and illustrate this via an application to gentamicin population pharmacokinetics in neonates.