IN VIVO INVESTIGATIONS USING MICRODIALYSIS SAMPLING

本项目的目标是开发微透析采样方法， 对重要系统的研究。微透析取样 通过在该部位植入短长度的透析纤维来实现 感兴趣用取样溶液缓慢灌注该纤维， 样品中的小分子量化合物扩散到纤维中 并被扫走以被收集用于分析。 虽然最初 为神经化学系统的脑内取样而开发，我们有 证明了血流微透析取样的实用性， 用于药代动力学研究的外周组织。 一种新的微透析探针设计将用于门静脉取样， 测定口服药物的生物利用度， 确定首过代谢的影响。 方法也将是 开发用于采样眼睛的玻璃体液作为重要的 药理学部位不能很好地由血药浓度代表。 取样这个网站还需要开发一个新的 微透析探针设计。皮肤采样方法的开发将 持续期间内的 需要增强的微量分析技术来支持开发 因为小体积、低浓度的样品 这一技术的结果。 将开发两个在线系统， 在微透析实验期间实现近实时分析。 在 第一个系统，微透析采样将耦合到快速微孔 液相色谱法 在第二个系统中，微透析取样将 与毛细管电泳在线耦合。 微透析系统中物质传输的基本方面将 也被调查。已经设计了一种体外流动装置， 模拟血流研究流体动力学条件下的微透析 条件用于校准探针以供体内使用的两种方法， 将研究最佳取样条件的参数。 基于微透析输送模式的校准技术将是 研究了取样组织校准的适用性。

The goal of this project is to develop microdialysis sampling methods for the study of pharmacologically important systems. Microdialysis sampling is accomplished by implanting a short length of dialysis fiber at the site of interest. This fiber is slowly perfused with a sampling solution such that small molecular weight compounds in the sample diffuse into the fiber and are swept away to be collected for analysis. While originally developed for intracerebral sampling of neurochemical systems, we have demonstrated the utility of microdialysis sampling of the blood stream and peripheral tissue for pharmacokinetic investigations. A new microdialysis probe design will be used to sample the portal vein to determine the bioavailability of orally administered drugs and to determine the effect of first-pass metabolism. Methods will also be developed for sampling the vitreous humor of the eye as an important pharmacological site not well represented by blood concentrations. Sampling this site will also require the development of a new microdialysis probe design. Development of dermal sampling methods will be continued. Enhanced microanalytical techniques are needed to support the development of microdialysis because of the small volume, low concentration samples resulting from this technique. Two on-line systems will be developed to achieve near real-time analysis during a microdialysis experiment. In the first system, microdialysis sampling will be coupled to fast microbore liquid chromatography. In the second system, microdialysis sampling will be coupled on-line to capillary electrophoresis. Fundamental aspects of mass transport in the microdialysis system will also be investigated. An in vitro flow apparatus has been designed to simulate the blood stream to study microdialysis under hydrodynamic conditions. Both methods for calibrating the probe for in vivo use and parameters for optimal sampling conditions will be investigated. Calibration techniques based on the delivery mode of microdialysis will be studied for applicability to calibration for sampling tissues.