OCULAR PHARMACOKINETICS OF FLUORESCENT DRUG ANALOGUES

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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.