IN VIVO INVESTIGATIONS USING MICRODIALYSIS SAMPLING

使用微透析取样进行体内研究

• 批准号: 2713723
• 负责人: CRAIG E LUNTE
• 金额: $ 12.81万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-06-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2713723
• 关键词: capillary electrophoresis; drug /agent; drug metabolism; embryo /fetus pharmacology; eye pharmacology; laboratory rat; liquid chromatography; mass spectrometry; microdialysis; pharmacokinetics; placental transfer

DESCRIPTION: The goal of this project is to develop microdialysis sampling techniques for investigating the factors that determine therapeutic drug bioavailability. Microdialysis sampling enables continuous monitoring of extracellular concentrations of compounds at specific biological sites in conscious animals. While initially developed for intracerebral sampling of neurochemical systems, the investigator has expanded the utility of the technique to the study of pharmacokinetics of therapeutic compounds in the blood stream and peripheral tissues. These techniques will be expanded to use microdialysis sampling to study the transport of compounds in vivo with an emphasis on transport across biological barriers. This will be accomplished through development in three areas: microdialysis probe calibration improved microanalytical techniques and development of microdialysis sampling procedures. The major impediment to the general applicability of microdialysis sampling is the lack of analytical methods that readily analyze the microvolume, low concentration, high ionic strength samples obtained. This need will be addressed in this project through the development of fast microbore LC methods. In particular, fast gradient microbore LC techniques and the use of nonporous packing materials will be investigated. Capillary electrophoresis is particularly attractive for analysis of dialysis samples although poor concentration sensitivity and limited compatibility with highly ionic samples is problematic. Both issues will be addressed through development of sample stacking technique applicable to high ionic strength samples. In addition a nanoflow electrospray interface will be built to provide CE-MS and direct on-line microdialysis -MS capabilities. Ultimately, microdialysis sampling will be used to study the transport of therapeutic compounds across biological barriers. Some work began during the past funding period on the study of transport across the dermis and the blood-brain barrier; this work will continue. A new emphasis on oral availability of drugs will be started by developing sampling techniques for the gastric and intestinal wall and the portal vein. Drug disposition into the ocular fluid across the placenta will also be examined.

描述：该项目的目的是开发微透析采样 研究确定治疗药物的因素的技术 生物利用度。 微透析采样可连续监视 特定生物位点的化合物细胞外浓度 有意识的动物。 最初开发用于脑内抽样的 神经化学系统，研究人员扩大了 研究治疗化合物药代动力学的技术 血流和周围组织。 这些技术将扩展到 使用微透析抽样研究化合物在体内的传输 强调跨生物障碍的运输。 这将是 通过三个领域的发展完成：微透析探测 校准改进了微分析技术和开发 微透析抽样程序。 一般的主要障碍 微透析采样的适用性是缺乏分析方法 很容易分析微伏，低浓度，高离子强度 获得的样品。 该项目将通过 快速微孔LC方法的开发。 特别是，快速梯度 Microbore LC技术和非孔包装材料的使用将是 调查。 毛细管电泳特别有吸引力 分析透析样品，尽管浓度较差，并且 与高离子样品的兼容性有限是有问题的。 这两个问题 将通过开发样品堆叠技术来解决 适用于高离子强度样品。 另外 电喷雾接口将用于提供CE-MS和直接在线直接 微透析-MS功能。 最终，微透析抽样将是 用于研究治疗化合物在生物学上的运输 障碍。 在过去的资金期间开始了一些工作 穿过真皮和血脑屏障；这项工作将 继续。 对毒品的口服可用性的新强调将由 开发胃壁和肠壁的采样技术以及 门静脉。 药物处置到整个胎盘上的眼液中 也将被检查。