Brunner Martin, Langer Oliver
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna--Allgemeines Krankenhaus, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
AAPS J. 2006 Apr 14;8(2):E263-71. doi: 10.1007/BF02854896.
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.
靶位点药代动力学（PK）的定量对于药物研发至关重要。临床微透析（MD）越来越多地用于描述各种分析物游离部分的药物分布和受体相PK。MD实验成本相对较低，并且在合适的分析方法下，几乎任何药物分子的靶组织PK都可以进行定量。MD的主要局限性在于，不经手术，脑、肺或肝脏等器官不易获取。最近，非侵入性成像技术，即正电子发射断层扫描（PET）或磁共振波谱（MRS），已可用于体内药物分布评估，并能在几乎每个人体器官中进行药物浓度测量。然而，MRS成像的空间分辨率较低，尽管PET能够以几毫米的空间分辨率监测区域药物浓度差异，但区分结合态和游离态药物或母体化合物与代谢物却很困难。此外，放射性示踪剂的开发既耗时又费力，需要特殊的专业知识，而且运行PET设备产生的辐射暴露和成本也不容忽视。最近MD与成像的互补应用使得能够利用这些不同技术的各自优势。总之，MD和成像技术提供了迄今为止尚未获得的药物分布数据。单独使用或联合使用，这些方法可能在未来的药物研发中发挥重要作用，有可能作为临床决策的转化工具。
