NEW METHODS FOR DETERMINATION OF PENTAMIDINE

测定喷他脒的新方法

• 批准号: 3422610
• 负责人: Thomas W. Bell
• 金额: $ 3.31万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-30 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3422610
• 关键词: chemical binding; chemical synthesis; drug receptors; fluorescent dye /probe; pentamidine

The aim of this project is to develop a chemical reagent that can be used to directly measure pentamidine in blood or other fluids from AMS patients undergoing therapy for Pneumocystis carinii pneumonia. This reagent is a synthetic organic molecule containing a dye that would fluoresce upon binding pentamidine. The reagent could be mixed with blood or lung lavage samples enabling determination of pentamidine concentration by spectrofluorometric assay. Alternately, the synthetic pentamidine receptor could be used to construct a fiber optic chemical sensor for measuring pentamidine reversibly in a flow system or in vivo. Pentamidine isethionate is currently the drug of choice for treatment of Pneumocystis carinii pneumonia, the leading killer of AIDS patients. It is also administered by inhalation to prevent recurrence of this AIDS-related disease. Pentamidine is toxic and its pharmacokinetics and optimum administration protocols have yet to be fully determined. Current methods for pentamidine measurement involve laboratory manipulation of blood extracts, requiring considerable time. The proposed analysis method would be fast and would involve minimum risk of HIV infection for personnel. The proposed project involves synthesis of several derivatives of a compound that has already been found to bind pentamidine in extraction and ion-selective electrode experiments. The fluorescent dye is to be introduced as part of the framework of this molecule. Variable functional groups will then be used to achieve the correct physical properties, enabling the synthetic receptor to bind pentamidine strongly, selectively and with a fluorescent response.

这个项目的目的是开发一种可以使用的化学试剂 直接检测AMS患者血液或其他体液中的五烷嘧啶 正在接受卡氏肺孢子虫肺炎的治疗。这种试剂是一种 含有一种染料的合成有机分子，这种染料会在 结合型五烷双胺。该试剂可以与血液或肺灌洗混合使用 样品可通过以下方法测定五胺盐的浓度 荧光分光光度分析。或者，合成的五烷双胺受体 可用于构建用于测量的光纤化学传感器 在流动体系中或在体内可逆地生成五烷双胺。 目前，异硫酸戊双胺是治疗慢性阻塞性肺疾病的首选药物 卡氏肺孢子虫肺炎是艾滋病患者的头号杀手。它是 也可吸入给药，以防止这种与艾滋病相关的复发 疾病。戊二甲双胺的毒性及其药代动力学及优化 管理方案尚未完全确定。当前的方法 对于五烷双胺的测量涉及到血液的实验室操作 提取物，需要相当长的时间。拟议的分析方法将 速度要快，并将使人员感染艾滋病毒的风险降至最低。 拟议的项目涉及合成一种新的 已被发现在提取和提取过程中与五烷胺结合的化合物 离子选择电极实验。荧光染料将是 作为该分子框架的一部分被引入。可变泛函 然后将使用组来实现正确的物理属性， 使合成的受体能够有选择地与五烷胺强烈结合 并有荧光反应。