Purchase this article with an account.
K. Ueda, A. Ohtori, K. Tojo; Effect of Pathologic Conditions on Ocular Pharmacokinetics. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5980.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Drugs are usually administered under pathological conditions that differ from normal conditions. Although ocular drug via topical instillation is widely studied and a number of pharmacokinetic models are developed, clear view on the drug movement in the eye is yet to come under disease conditions. In this study, we report the drug transport routes in the abnormal eye after topical instillation by a diffusion model for the pharmacokinetics of ocular drug delivery.
The in vivo experimental data of ciprofloxacin and ofloxacin after topical instillation were compared with the simulated time course of concentration in aqueous and vitreous humors by a pharmacokinetic model, a modified cylindrical eye model. The model parameters were defined as the diffusion and partition coefficient which could be evaluated from the correlation equations previously determined in terms of the molecular weight and octanol/buffer partition coefficient. Additionally, the pharmacokinetics in the inflamed eye was simulated by changing the barrier capacity of surrounding membranes.
The drug concentrations of normal eye were well correlated with in vivo experiments. The drug concentrations of inflamed eye could be well described by increasing the penetration across the surrounding membranes. These results showed the good agreement between the simulated results and the in vivo experiments. The concentration in aqueous and vitreous humors of the inflamed eye was higher than the value of the normal eye. Additionally, the drug concentration gradient was observed in the inflamed eyes, because the drug elimination from sclera/retina was enhanced by the inflammation.
The present diffusion model could analyze the pharmacokinetics of ocular drug in both normal and diseased conditions. The model could also confirm the routes of elimination in the eye.
This PDF is available to Subscribers Only