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K.J. Tojo; PC Simulator for Ocular Pharmacokinetics: Virtual Ocular PK . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5085.
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© ARVO (1962-2015); The Authors (2016-present)
1) To develop PC simulator for analyzing the ocular pharmacokinetics and pharmacodynamics following a variety of ocular drug delivery systems. 2) To predict the local concentration distribution in the eye including anterior and posterior aqueous chambers, lens, vitreous body and the other tissues. 3) To compare the calculated concentration profiles following various ocular drug deliveries with the in vivo animal and clinical data.
A pharmacokinetic model of ocular drug delivery has been developed for describing the elimination and distribution of ocular drugs in the eye. The model, based on Fick’s second law of diffusion, assumes a modified cylindrical eye with three pathways for drug transport across the surface of the eye: the anterior aqueous chamber, the posterior aqueous chamber and the retina/choroids/scleral membranes covering the vitreous body. The model parameters such as the diffusion coefficient and the partition coefficient in various eye tissues were evaluated from the in vitro membrane penetration experiments using a side–by–side diffusion cell system.
The drug concentration distribution in the eye was well described by the present model for both topical instillation and systemic administration. The diffusion coefficient and the partition coefficient in the ocular tissues were determined from the in vitro penetration experiment using animal models including rabbit, bovine and pig. With the model parameters, the present ocular pharmacokinetic model can be used for evaluating the clinical performance of various ocular drug delivery systems.
The present computational "virtual eye" approach is useful to simulate the effects of various factors not only for the delivery system design but for the physiological or individual differences of the eye. Using this computer model, we may be able to reduce significantly both in vivo animal experiments and clinical trials by designing a rational and effective protocol for clinical studies.
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