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Y. Shikamura, A. Ohtori, K. Tojo; Concentration Distribution in the Posterior Ocular Tissue After Drug Instillation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1824.
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To evaluate the drug concentrations in the posterior segments of the eye after instillation of a drug solution.
One drop of 0.3% ofloxacin solution was instilled in the eye of rabbits. At 1, 2 and 3 hours after instillation, the eye was enucleated and frozen. The frozen eyes were then divided into three sections: anterior, central and posterior segments. The concentrations of ofloxacin in ocular tissues were determined by high performance liquid chromatography. The experimental concentration profile in the vitreous body was compared with the ones simulated by using a pharmacokinetic model of ocular drug delivery based on the diffusion/partition model.
The concentration of ofloxacin in each section of posterior ocular tissues, analyzed at 1 hour after instillation, indicated that ofloxacin distributed to the posterior ocular tissues: sclera, retina-choroid and vitreous body. The elimination profiles of ofloxacin in the posterior ocular tissues suggested that the ofloxacin concentration of the posterior segment was higher than that of the central segment in the vitreous body at 3 hours after instillation. The finding of the concentration distribution in vivo tended to agree with the simulated profiles on the based of the ocular pharmacokinetic model in which the diffusion across the vitreous body surface was predominant.
The instilled drug quickly distributes to the posterior segments of the vitreous body. The major route of this distribution is assumed to diffusion through the surrounding tissues of the vitreous body. The concentration in the posterior vitreous tissue does not equally distribute shortly after instillation. This may suggest that the pharmacodynamic response should be analyzed not by the average concentration in the vitreous body but by the site-dependent local concentrations.
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