OCULAR PHARMACOKINETICS OF FLUORESCENT DRUG ANALOGUES

局部给药后一系列荧光团的眼内动力学 将通过测量变化来研究对兔眼的应用 随着时间的推移，在角膜和水的浓度与一个特殊的 设计的裂隙灯荧光计。 类似的测量将在 离体角膜，其中动态测量角膜中的荧光分布， 将用改进的镜面反射显微镜制作角膜。 将确定染料的以下生物学参数： 上皮渗透性、溶解性、通过时间、内皮 渗透性、基质溶解度、扩散速率。 研究了不同浓度的聚合物的油水分配系数、离子电荷和分子量 这些染料将与它们的生物学特性相关联， 建立有助于发展的关系， 具有改善的药代动力学性质的治疗药物。 晶体透镜中荧光团动力学的测量 将包括在完整家兔的测量中，以便 确定它在多大程度上可以作为药物的储存库， 使前房中出现的浓度低谷变平 应用程序之间。 随着年龄的增长，人角膜中的自然荧光的变化， 以及在疾病中，将使用裂隙灯荧光光度计 使用不同的激发波长。 希望能找到一个 年龄或病理状况诊断的可量化标记。 宿主年龄对角膜移植物老化的影响将 接受检查。

The intraocular kinetics of a range 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 specially designed slit-lamp fluorometer. Similar measurements will be made on the isolated cornea, where dynamic measurements of fluorescent profiles in the cornea will be made with a modified specular microscope. The following biological parameters for the dyes will be determined: Epithelial permeability, solubility, transit time, endothelial permeability, stromal solubility, diffusion rate. The oil-water partition coefficient, ionic charge and molecular weights of the dyes will be correlated with their biological properties in an attempt to establish relationships that will assist in the development of therapeutic drugs with improved pharmacokinetic properties. 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 between applications. The changes in the natural fluorescence in the human cornea with age, as well as in disease, will be followed with the slit-lamp fluorophotometer using different excitation wavelengths. It is hoped to identify a quantifiable marker for age or the diagnosis of pathological conditions. The influence of the age of the host on the aging of a corneal graft will be examined.