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Jihwang Lee, Hye kyoung Hong, Se Joon Woo, Hyuncheol Kim; Simulating Distribution of Drugs Depending on logP Values in a Rabbit Eye Model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6416.
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© ARVO (1962-2015); The Authors (2016-present)
The objective of this study is estimating the distribution of two drugs, which have different solubility in the vitreous, after the intravitreal injection by simulating the 3-D mathematical model in a rabbit eye.
Several ocular tissues including the vitreous were isolated. The diffusion coefficients of two different drugs through the isolated tissues were determined by using the Ussing chamber. A 3-dimensional finite element mathematical eye model were developed and the convection and diffusion equations were applied to determine the aqueous humor flow and drug distribution in the eye with the experimentally determined diffusion coefficients.
The average velocity of the aqueous humor through the retina was 3.66×10-7 m/s which is comparable to the previously reported data. The simulation study demonstrated that the concentration of intravitreally administered more hydrophobic drug (Brimonidine) was 3.6 and 4.4 fold higher than that of more hydrophilic drug (Ganciclovir) at 6 and 12 hours in the vitreous, respectively. The vitreal half-lives of Ganciclovir and Brimonidine were determined to be 5 and 12 hours, indicating that the more hydrophilic drug (Ganciclovir) were eliminated both anteriorly and posteriorly more easily than the more hydrophobic drug (Brimonidine).
To the best of our knowledge, it is the first study to determine the diffusion coefficients for the two drugs, which show different solubility in water, and compare the pharmacokinetics of different solubility drugs with the 3-D mathematical eye mode. More water-soluble drug in the vitreous showed less elimination rate and longer half-life.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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