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Browsing by Subject "farmakokineettinen simulaatiomalli"

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  • Soini, Esa-Matti (2015)
    Posterior segment ocular diseases, such as age-related macular degeneration and diabetic retinopathy, can cause irreversible damage to the retina and visual impairments. Topical eye drop administration can be used for the treatment of anterior segment diseases, but it is not possible to get therapeutic drug concentrations in the posterior segment of the eye via topical route. Currently, intravitreal injections and implant are widely used for the treatment of posterior segment diseases. However, intravitreal administration can cause pain and discomfort, and frequent intravitreal administration can lead to, for example, retinal detachment and endophthalmitis. Therefore, safer and more patient friendly drug delivery method would be needed. After systemic administration, blood-aqueous barrier and bloodretinal barrier hinder the diffusion of drugs to the intraocular tissues. The aim of the experimental part was to develop a pharmacokinetic simulation model that could be used to predict the distribution of drugs into the eye after systemic administration. Such a model would be a very useful tool in drug development. The prediction accuracy of the model was tested with ten drugs. Concentrations in the vitreous and blood after systemic administration in rabbits has been published for these drugs. On average the prediction accuracy of the model was quite good: the simulated AUC of the drug concentration in the vitreous was 125 % and Cmax 117 % of the measured reference value. However, there was a significant amount of variation in the results. The lowest simulated AUC was 15 % and the highest simulated AUC was 403 % of the measured reference value. Therefore, the model is not yet realiable enough to be used as a tool in drug development. It might be possible to increase the prediction accuracy of the model by incorporating active transport into it and by using 2-compartment model to simulate systemic pharmacokinetics.