Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Altern Lab Anim. 2009 Sep;37 Suppl 1:57-9. doi: 10.1177/026119290903701S08.
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.
药物分布的体内评估长期以来一直被视为药代动力学的“被遗忘的亲属”，主要是由于缺乏适当的方法。研究长期以来一直局限于测量相对容易获得的生物样本中的药物浓度，或进行间接建模。然而，这些方法获得的数据导致了对药物分布和靶部位递送的相当大的混淆，因为它们的解释受到了几个误解的影响，例如缺乏生理输入到药代动力学模型，错误地认为组织是一个均匀的基质，以及认为存在于各种组织空间中的整个药物分数发挥药理活性的观念。如今，可以通过微透析术相对廉价、微创和可重复地测量药物分布到定义明确的组织隔室 - “细胞间空间液”，这是许多药物的生物相。
