ANTIVIRAL DRUG KINETICS IN VITREOUS USING MICRODIALYSIS

使用微透析进行玻璃体内抗病毒药物动力学

• 批准号: 2391745
• 负责人: Ashim K. Mitra
• 金额: $ 14.49万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2391745
• 关键词: acyclovir; cytomegalovirus; dosage; eye infections; eye pharmacology; ganciclovir; high performance liquid chromatography; laboratory rabbit; microdialysis; pharmacokinetics; sodium potassium exchanging ATPase; vitreous body

DESCRIPTION (adapted from Abstract): The broad, long-term objective of the proposed research is to develop a rational intravitreal and systemic drug delivery strategy for treatment of cytomegalovirus (CMV) and herpes simplex virus (HSV) infections. In order to accomplish this, the Principal Investigator has employed microdialysis to sample continuously the vitreous compartment in order to obtain detailed pharmacokinetic information. Preliminary information from the experiments conducted by the Investigator indicates the half-life of ganciclovir in the vitreous is two hours in albino rabbits whereas it is 6 hours in pigmented rabbits. The pigmented rabbit will be used for the proposed study. The microdialysis technique and half-life findings form a basis for the development of controlled long-term intravitreal delivery systems for treatment of infections such as CMV retinitis. This project will attempt to prolong the therapeutic levels of acyclovir and ganciclovir from intravitreal injection by entrapping the drug into biodegradable and biocompatible microspheres. Additional specific aims of this project are to elucidate the dose, Na, K ATPase and metabolic energy dependence, if any, of the vitreous elimination kinetics of purine antiviral analogs.

描述（根据摘要改编）： 拟议的研究是开发合理的玻璃体室内和全身性 用于治疗巨细胞病毒（CMV）和疱疹的药物输送策略 单纯形病毒（HSV）感染。为了实现这一目标， 首席研究者已采用微透析来连续采样 玻璃体室以获得详细的药代动力学 信息。来自实验的初步信息 研究者指示玻璃体中Ganciclovir的半衰期 在白化兔子中是两个小时，而色素为6小时 兔子。色素的兔子将用于拟议的研究。这 微透析技术和半衰期的发现构成了该技术的基础 开发受控的长期玻璃体内输送系统 治疗CMV视网膜炎等感染。这个项目将尝试 从 玻璃体内注射通过将药物置于可生物降解和 生物相容性的微球。该项目的其他具体目标是 为了阐明剂量，na，k atpase和代谢能依赖性，如果 嘌呤抗病毒类似物的玻璃体消除动力学。