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

Abstract

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.

Extended Pharmacokinetic Model of the Rabbit Eye for Intravitreal and Intracameral Injections of Macromolecules: Quantitative Analysis of Anterior and Posterior Elimination Pathways

“…More recently, CFD models have been built for the complete eye enabling simultaneous evaluation of drug kinetics in the anterior and posterior segments of the eye after IVT and topical application (11,(20)(21)(22)(23)(24)(25). The most comprehensive study on IVT administration was published by Missel (11) who built anatomically accurate models for human, rabbit and monkey eyes based on MRI, and validated the rabbit model using published in vivo data on six compounds with a wide range of molecular weights (0.3-157 kDa).…”

Novel Lutein Loaded Lipid Nanoparticles on Porcine Corneal Distribution

“…The proposed mechanism of HP β CD combined with NLC in the enhanced lutein accumulation includes the following possibility. In the process of corneal permeation, the drug should be released from the vehicles followed by partition or absorption into the cornea [35]. The diffusion rate of drugs from the vehicle is essential for the corneal accumulation of drugs [36].…”

Ocular instillation toxicity study: current status and points to consider on study design and evaluation

“…For example, Tojo (2004) reported a PK model for ocular drug delivery. In silico drug penetration was reported in the posterior eye tissues after topical instillation in rabbits (Shikamura et al, 2011). In addition, Ueda et al (2010) reported an ocular diffusion model of antimicrobial drugs in normal and diseased eyes.…”