OCULAR PHARMACOKINETICS OF FLUORESCENT DRUG ANALOGUES

眼内动力学的各种荧光团后局部 将通过测量变化来研究对兔眼的应用 在角膜和房水中浓度随时间变化， 荧光计。 穿过角膜的扩散和运输的ism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 改良的镜面反射显微镜，和2）通过组织的转移速率 将在设计成避免边缘效应的腔室中进行。 将确定染料的以下生物学参数： 上皮渗透性，内皮渗透性，扩散速率， 基质、穿过各层的通过时间和平衡 分布在水层和各层之间。 染料的亲油性、电离度和分子量 将与上述生物学特性相关联， 建立关系，这将有助于发展的治疗 具有改善的药代动力学特性的药物。 从商业来源获得的荧光团将被纯化。 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得均匀， 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.