PHARMACOKINETIC ANALYSIS FOR ADEQUATE MEDICATION-USE IN OPHTHALMOLOGY

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Purpose of this research is to develop the pharmacokinetic model for drug disposition in the eye after ocular application.(1) The penetrations of various drugs were measured across the isolated ocular membranes of the albino rabbit using a two-chamber glass diffusion cell. As the results, the obtained penetration profiles were analyzed based on a diffusion model for the infinite dose system.(2) The drug dispositions in the precorneal area of the rabbits after instillation and the drug dispositions in the aqueous humor of rabbits after injection into the aqueous chamber of the eye were characterized by mathematical model. These dispositions were dependent on drug lipophilicity and molecular weight.(3) On the basis of these results, the compartment model including the diffusion process was developed to describe the drug dispositions in the eye after instillation. The kinetic model well described the drug concentrations in the aqueous humor after instillation in anesthetized rabbits that … More was used as a model of tear secretion deficiency. These results indicated the propriety of the kinetic model.(4) In order to expand the application of the kinetic model, the drug dispositions in the eye of rabbits were analyzed using the kinetic model after application in the form of viscous vehicle, polymeric insert, lipophilic prodrug, and absorption promoting formulation. The simulation based on the modified model including the diffusion process well described the aqueous humor concentration of drugs after application in the form of viscous vehicle and polymeric insert. The apparent permeability parameters of drugs were estimated by the kinetic model after application in the form of lipophilic prodrug and absorption promoting formulation.(5) The kinetic model and the parameters for human were developed using human data previously reported.Thus, the kinetic model and parameters are effective to develop the ocular drug delivery systems and estimate the adequate regimen for ophthalmic medication. Less