Application of microdialysis for pharmacokinetic-pharmacodynamic modelling

Abstract

Pharmacokinetic–pharmacodynamic (PK–PD) modelling describes the relationship between the pharmacokinetics and pharmacodynamics of a drug allowing the prediction of clinically relevant parameters. PK–PD modelling has several advantages over classical dose–response studies because it allows a better pharmacodynamic characterisation of drugs and screening of dosage– regimen. However, PK–PD studies are limited by the need for simultaneous measurement of drug tissue levels and corresponding pharmacological effects at multiple time points. The microdialysis technique is a unique research tool that allows the simultaneous determination of unbound concentrations of drugs at several tissues and its action on biochemical and clinical markers during several hours and days. Therefore, microdialysis sampling is an attractive methodology for PK–PD studies. The aim of this review is to describe the applicability of the microdialysis technique for PK–PD modelling of therapeutic agents, including the description of PK–PD modelling concepts, an overview of the microdialysis technique and the analysis of PK–PD studies using microdialysis sampling both in the preclinical and clinical setting.