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发布日期: Jul 17, 2019
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Physiologically based ocular pharmacokinetic modeling using computational methods - ScienceDirect

Highlights.•Reducing dose volume at constant amount dosed increases topical drug bioavailability.•Thermal convection renders the aqueous humor a well-mixed compartment.•After an initial distribution phase, drug elimination from the eye is first order.•Choroidal drug clearance can be modeled using a regional volumetric sink.•Drug physical properties affect the anterior/posterior pathway balance for clearance.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).