Some Considerations on the Design of Population Pharmacokinetic Studies

Abstract

The goal of this manuscript is to introduce a framework for consideration of designs for population pharmacokinetic orpharmacokinetic-pharmacodynamic studies. A standard one compartment pharmacokinetic model with first-order input and elimination is considered. A series of theoretical designs are considered that explore the influence of optimizing the allocation of sampling times, allocating patients to elementary designs, consideration of sparse sampling and unbalanced designs and also the influence of single vs. multiple dose designs. It was found that what appears to be relatively sparse sampling (less blood samples per patient than the number of fixed effects parameters to estimate) can also be highly informative. Overall, it is evident that exploring the population design space can yield many parsimonious designs that are efficient for parameter estimation and that may not otherwise have been considered without the aid of optimal design theory.