OCULAR PHARMACOKINETICS OF FLUORESCENT DRUG ANALOGUES

多种荧光团局部用药后的眼内动力学 将通过测量变化来研究其在兔眼中的应用 随着时间的推移，裂隙灯在角膜和房水中浓缩 荧光计。通过角膜的扩散和弥散运输将是 通过体外研究进一步研究，其中1)动态测量 角膜中的荧光团浓度分布将用 改进的镜面显微镜，以及2)跨组织的转移率 将在一个为避免边缘效应而设计的腔室中制作。 将确定染料的下列生物参数： 上皮通透性，内皮通透性，扩散速率 基质、跨不同层的传输时间和平衡性 在水层和各层之间的分布。 染料的亲油性、电离度和相对分子质量 将与上述生物特性相关联，以尝试 建立有助于开发治疗方法的关系 具有改进的药代动力学特性的药物。 从商业来源获得的荧光团将被提纯。 晶状体中荧光团动力学的测量 将包括在对完好的兔子的测量中，以便 确定它在多大程度上可以作为药物的储存库 甚至是在前房出现的集中的低谷 在局部应用之间。

The intraocular kinetics of a variety of fluorophores after topical application to the rabbit eye will be investigated by measuring the changes with time in concentration in the cornea and aqueous with a slit-lamp fluorometer. Diffusion and ism of transport across the cornea will be further investigated by in vitro studies where 1) dynamic measurements of the fluorophore concentration profile in the cornea will be made with a modified specular microscope, and 2) the rate of transfer across the tissue will be made in a chamber designed to avoid edge effects. The following biological parameters for the dyes will be determined: Epithelial permeability, endothelial permeability, diffusion rate in stroma, transit times across the various layers, and equilibrium distribution between aqueous and various layers. The lipophilicity, degree of ionization, and molecular weights of the dyes will be correlated with the above biological properties in an attempt to establish relationships that will assist in the development of therapeutic drugs with improved pharmacokinetic properties. The fluorophores obtained fran commercial sources will be purified. Measurements of the kinetics of the fluorophores in the crystalline lens will be included in the measurements on the intact rabbit in order to determine to what extent it can serve as a reservoir for drugs which will even out the troughs in concentration in the anterior chamber that occur in between topical applications.