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Yuko Shikamura, Akira Ohtori, Kakuji Tojo; Drug Penetration to the Posterior Vitreous Body after Topical Instillation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3242.
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In our previous in vivo rabbit pharmacokinetic studies, the drug concentration at the posterior vitreous body initially decreased with time after topical instillation, and thereafter the concentration increased. The purpose of this study is to analyze this interesting time course of vitreous body concentration by the mathematical simulation model on the basis of the diffusion model.
The ocular pharmacokinetic model developed is based on the Fick’s law of diffusion and a modified cylindrical model. The model parameters, the diffusion coefficient in various ocular tissues, are independently determined from in vitro experiment. The concentration distribution of ofloxacin in the eye was calculated after solving the governing partial differential equation. The calculated profiles were then compared with the in vivo experimental profiles.
In silico simulation for ocular pharmacokinetics indicated that the drug penetration to the posterior vitreous body was determined by three major pathways after topical instillation: (1) initial transscleral penetration, (2) middle transcorneal penetration and (3) late transretinal penetration. The in vivo penetration profile in the posterior vitreous body was clearly described by a series of contribution of these three pathways.
The present in silico study suggests that the instilled drugs reach the posterior vitreous body via the conjunctiva/sclera and slowly via the cornea penetration and systemic circulation. The theoretically simulated profile was very consistent with the in vivo rabbit experiments.
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