AI Article Synopsis
- The study aimed to create a computer-based model to understand how the eye drop FK962 behaves in the eye, specifically for treating choroid/retinal diseases.
- It involved testing FK962 in rabbits and measuring how well it moves through different layers of the eye, as well as its effect on retinal cells.
- The results showed that the model accurately predicts drug concentrations in the eye and suggests an effective dosing schedule for FK962, which could be beneficial for clinical trials focusing on retinal health.
Article Abstract
Purposes: To establish the in silico ocular pharmacokinetic modeling for eye drops, and to simulate the dose regimen for FK962 in human choroid/retinal diseases.
Methods: Pharmacokinetics for FK962 in vivo was performed by a single instillation of drops containing 0.1% C-FK962 in rabbit eyes. Permeation of FK962 across the cornea, sclera, and choroid/retina was measured in vitro. Neurite elongation by FK962 was measured in cultured rat retinal ganglion cells. Parameters from the experimental data were used in an improved in silico model of ocular pharmacokinetics of FK962 in man.
Results: The mean concentration of FK962 in ocular tissues predicted by in silico modeling was consistent with in vivo results, validating the in silico model. FK962 rapidly penetrated into the anterior and posterior segments of the eye and then diffused into the vitreous body. The in silico pharmacokinetic modeling also predicted that a dose regimen of 0.0054% FK962 twice per day would produce biologically effective concentrations of FK962 in the choroid/retina, where FK962 facilitates rat neurite elongation.
Conclusions: Our in silico model for ocular pharmacokinetics is useful (1) for predicting drug concentrations in specific ocular tissues after topical instillation, and (2) for suggesting the optimal dose regimens for eye drops. The pharmacodynamics for FK962 produced by this model may be useful for clinical trials against retinal neuropathy.
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| http://dx.doi.org/10.1089/jop.2016.0136 | DOI Listing |
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