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The purpose of this study was to analyze drug pharmacokinetics in the posterior eye tissues after topical instillation. For the in vivo study, the concentrations of ofloxacin in rabbit ocular tissues were analyzed by high performance liquid chromatography at 1, 2, and 3 h after instillation. For the in silico simulation, the concentration distribution of ofloxacin in the eye was calculated by the ocular pharmacokinetic model based on the diffusion/partition model. The simulated profiles were then compared with the in vivo experimental findings. In the in vivo study, the drug concentration in the posterior vitreous body initially decreased with time after topical instillation, and thereafter, the concentration increased. The in silico simulation of ocular pharmacokinetics indicated that the drug penetration of the posterior vitreous body was determined by three major pathways: (1) the initial transscleral penetration, (2) the intermediate transcorneal penetration, and (3) the late transretinal penetration. The in vivo findings were well described by a series of contributions by these three pathways. In conclusion, the present in vivo and in silico studies suggest that the instilled drugs initially reached the posterior vitreous body by diffusion through the sclera and then later by corneal penetration and systemic circulation.

Drug Penetration of the Posterior Eye Tissues after Topical Instillation: In Vivo and in Silico Simulation