Physiologically based ocular pharmacokinetic modeling using computational methods

By explicitly representing ocular anatomy, computational fluid dynamic simulation methods model drug mass transport both within and between ocular tissue regions, providing reliable animal-to-human translation of bioavailability. Here, we apply physiologically based models to simulate ocular drug administration. A non-anatomical model is used that applies a simple theorem for calculating ocular bioavailability from a topical dose. A computational fluid dynamic model is also described that incorporates ocular physiology in anatomical models for rabbit, monkey and man. This second method applies material properties and boundary conditions for various tissues enabling simulation of fluid flows, pressures, temperatures, convection, and drug advection following various modes of administration. The method provides a regional distribution with a given tissue not available using standard compartmental models, and enables translation of results from animal experiments into predictions for human ocular pharmacokinetics (PK).