AAPS-FDA workshop white paper:: Microdialysis principles, application and regulatory perspectives
AAPS-FDA workshop white paper:: Microdialysis principles, application and regulatory perspectives
复制标题
DOI：
10.1007/s11095-006-9206-z
复制
发表时间：
2007-05-01
影响因子：
3.7
通讯作者：
Yeo, Helen
中科院分区：
文献类型：
--
作者：
Chaurasia, Chandra S.;Mueller, Markus;Yeo, Helen
药物开发和医疗实践中的许多决策都是基于测量内源性和外源性分子的血液浓度。然而，大多数生物化学和药理学事件发生在组织中。此外，除了少数明显的例外，大多数药物不在血流中发挥作用，而是在药物必须从中央室分布到其中的限定靶组织中发挥作用。因此，长期以来，评估组织药物化学被认为是提供临床有意义数据的更合理的方法，而不是从血液样本中获得信息。更具体地说，通常是细胞外（间质）组织空间与药物的作用部位（生物相）最密切相关。目前，微透析（mu D）是唯一可用的明确提供细胞外空间数据的工具。尽管mu D作为临床前和临床工具已经存在了二十年，但从方法学和监管角度来看，mu D在药物研发中的使用仍然存在不确定性。为了减少这种不确定性，并概述mu D在临床前和临床环境中的原理和应用，2005年11月在美国田纳西州纳什维尔举行了AAPS-FDA研讨会。来自学术界、工业界和监管机构的利益攸关方介绍了他们对mu D作为药物研究和开发工具的看法。
Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (mu D) is the only tool available that explicitly provides data on the extracellular space. Although mu D as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of mu D in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of mu D in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on mu D as a tool in drug research and development.