Monitoring Tissue Drug Levels by Clinical Microdialysis
The in vivo assessment of drug distribution has long been treated as a “forgotten relative” of pharmacokinetics, mainly due to a lack of appropriate methodology. Research was long restricted to the measurement of drug concentrations from biological specimens that are relatively easy to obtain, or to indirect modelling. However, data obtained by these approaches have resulted in considerable confusion about drug distribution and target site delivery, as their interpretation was flawed by several misconceptions, such as the lack of physiological input to pharmacokinetic models, the erroneous view that a tissue is a uniform matrix, and the notion that the entire drug fraction present in various tissue spaces exerts pharmacological activity. Today, drug distribution to the well defined tissue compartment — “interstitial space fluid”, the biophase for many drugs — can be measured relatively cheaply, minimally invasively, and reproducibly, via microdialysis.