Population pharmacokinetics meets microdialysis: benefits, pitfalls and necessities of new analysis approaches for human microdialysis data

Pharmacokinetic (PK) data originating from human microdialysis studies have by now most commonly been analysed using noncompartmental analysis or the standard two-stage population approach. During the last decades, additional modelling strategies for PK data have been developed, which also seem apt for the analysis of microdialysis data. The present opinion article gives an overview of the three approaches of nonlinear mixed-effects (NLME) modelling, physiologically-based pharmacokinetic (PBPK) modelling and a combined population PBPK modelling approach (PPBPK) as well as their application within the field of microdialysis in humans. Potential benefits and pitfalls of the different approaches will be outlined and exemplified, complemented by modelling prerequisites to be met on the part of principal investigators, bioanalysts and documentalists involved in a microdialysis study. In summary, the combination of microdialysis as the method of choice for measuring unbound drug concentrations in peripheral tissues and the presented modelling strategies seems a promising way to enhance the understanding of drug disposition at the target site of drugs and might thus contribute to a more rational use of medicines.