OCULAR PHARMACOKINETICS OF FLUORESCENT DRUG ANALOGUES

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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.