Chaurasia Chandra S, Müller Markus, Bashaw Edward D, Benfeldt Eva, Bolinder Jan, Bullock Ross, Bungay Peter M, DeLange Elizabeth C M, Derendorf Hartmut, Elmquist William F, Hammarlund-Udenaes Margareta, Joukhadar Christian, Kellogg Dean L, Lunte Craig E, Nordstrom Carl Henrik, Rollema Hans, Sawchuk Ronald J, Cheung Belinda W Y, Shah Vinod P, Stahle Lars, Ungerstedt Urban, Welty Devin F, Yeo Helen
Division of Bioequivalence, Office of Generic Drugs, Food and Drug Administration, Rockville, MD, USA.
Pharm Res. 2007 May;24(5):1014-25. doi: 10.1007/s11095-006-9206-z. Epub 2007 Mar 27.
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 (microD) is the only tool available that explicitly provides data on the extracellular space. Although microD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of microD 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 microD 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 microD as a tool in drug research and development.
药物研发和医学实践中的许多决策都基于对内源性和外源性分子血液浓度的测量。然而，大多数生物化学和药理学事件都发生在组织中。此外，除了少数明显的例外情况，大多数药物并非在血液中发挥作用，而是在特定的靶组织中发挥作用，药物必须从中央隔室分布到这些靶组织中。因此，长期以来，评估组织药物化学一直被视为一种更合理的方式，以提供具有临床意义的数据，而不是从血样中获取信息。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）关系最为密切。目前，微透析（microD）是唯一可明确提供细胞外空间数据的工具。尽管微透析作为一种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，微透析在药物研发中的应用仍存在不确定性。为了减少这种不确定性，并概述微透析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一次AAPS - FDA研讨会。来自学术界、工业界和监管机构的利益相关者就微透析作为药物研发工具发表了他们的看法。
