Development and implementation of the population Fisher information matrixfor the evaluation of population pharmacokinetic designs

In population pharmacokinetic studies, the precision of parameter estimates is dependent on the population design. Methods based on the Fisher informa tion matrix have been developed and extended to population studies to evalu ate and optimize designs. In this paper we propose simple programming tools to evaluate population pharmacokinetic designs. This involved the developm ent of an expression for the Fisher information matrix for nonlinear mixed- effects models, including estimation of the variance of the residual error. We implemented this expression as a generic function for two software appl ications: S-PLUS and MATLAB. The evaluation of population designs based on two pharmacokinetic examples from the literature is shown to illustrate the efficiency and the simplicity of this theoretic approach. Although no opti mization method of the design is provided, these functions call be used to select and compare population designs among a large set of possible designs , avoiding a lot of simulations. (C), 2001 Elsevier Science Ireland Ltd. Al l rights reserved.