Microdialysis versus other techniques for the clinical assessment of in vivo tissue drug distribution.
Quantification of target site pharmacokinetics (PK) is crucial for drug discovery and development. Clinical microdialysis (MD) has increasingly been employed for the description of drug distribution and receptor phase PK of the unbound fraction of various analytes. Costs for MD experiments are comparably low and given suitable analytics, target tissue PK of virtually any drug molecule can be quantified. The major limitation of MD stems from the fact that organs such as brain, lung or liver are not readily accessible without surgery. Recently, non-invasive imaging techniques, i.e. positron emission tomography (PET) or magnetic resonance spectroscopy (MRS), have become available for in vivo drug distribution assessment and allow for drug concentration measurements in practically every human organ. Spatial resolution of MRS imaging, however, is low and although PET enables monitoring of regional drug concentration differences with a spatial resolution of a few millimetres, discrimination between bound and unbound drug or parent compound and metabolite is difficult. Radiotracer development is furthermore time and labour intensive and requires special expertise and radiation exposure and costs originating from running a PET facility cannot be neglected. The recent complementary use of MD and imaging has permitted to exploit individual strengths of these diverse techniques. In conclusion, MD and imaging techniques have provided drug distribution data that have so far not been available. Used alone or in combination, these methods may potentially play an important role in future drug research and development with the potential to serve as translational tools for clinical decision making.
Brunner
Martin
M
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna--Allgemeines Krankenhaus, Waehringer Guertel 18-20, A-1090 Vienna, Austria. martin.brunner@meduniwien.ac.at
Langer
Oliver
O
D001706:Biopsy; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D017551:Microdialysis / Q000379:methods*; D010599:Pharmacokinetics; D049268:Positron-Emission Tomography; D012463:Saliva / Q000737:chemistry; D012867:Skin / Q000737:chemistry; D014018:Tissue Distribution