Application of microdialysis and modelling approaches to predict drug concentration at the site of action

Accurate quantification of drug concentrations at the site of action is essential for understanding pharmacological efficacy and optimising therapeutic strategies. Conventional pharmacokinetic (PK) assessments, which primarily rely on plasma drug concentrations, often fall short in capturing the unbound, pharmacologically active drug levels within target tissues. Microdialysis is a minimally invasive technique that enables real-time sampling of extracellular fluid and has emerged as a valuable method for measuring local, unbound drug concentrations in tissues such as the brain, muscle, skin and tumours. The integration of microdialysis with advanced modelling approaches, including physiologically based PK and population PK, and compartmental models, has markedly enhanced our ability to characterise drug distribution, assess tissue penetration and establish PK/pharmacodynamic relationships. This review outlines the fundamental principles of microdialysis and the evolution of modelling strategies used to analyse tissue-specific PK data. Through illustrative case studies involving antibiotics, central nervous system agents and anticancer therapies, we demonstrate the translational value of microdialysis-modelling integration from preclinical research to clinical application. While technical and methodological challenges remain, the combined use of microdialysis and modelling is increasingly supported by regulatory authorities as part of model-informed drug development. Ongoing advances in biosensor technologies, real-time analytical platforms and machine learning are poised to further strengthen this field, facilitating personalised treatment approaches and streamlining the drug development process.