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K.-S. Vellonen, E. Järvinen, A. Urtti; Kinetic Simulation of Active Drug Transport in the Cornea. Invest. Ophthalmol. Vis. Sci. 2010;51(13):696. doi: https://doi.org/.
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Topically applied ocular drugs may be absorbed by simple diffusion or active transport. Corneal epithelium expresses several influx and efflux transporters that influence drug permeation. We simulated the importance of active corneal transport in different cases.
Compartmental ocular models with tear fluid, corneal epithelium and anterior chamber compartments were built using Stella® 9.0.1 program. Ocular bioavailability and drug concentrations in aqueous humor were simulated. Simulations were carried out for hydrophilic and lipophilic compounds with different affinities (Km) and maximum velocities (Vmax) of active influx and efflux. Impact of drug release rate from formulation was also simulated.
Fast drug loss from the pre-corneal space (by drainage or conjunctival systemic absorption) and passive diffusion in the corneal epithelium were the most significant determinants of ocular bioavailability. Active transport has the most prominent effect on absorption when the drug has slow passive diffusion and/or small dose. High initial drug concentration after instillation and rapid clearance from the tear fluid clearly diminish the role of active transport in ocular drug absorption. However, transporters, especially influx carriers, may have significant effect on the bioavailability when the drug is administered with topical controlled release formulation.
Kinetic simulation model is a useful tool for probing transporter effects on ocular drug absorption.
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