Ocular Physiologically Based Pharmacokinetic Modeling for Ointment Formulations
Maxime Le Merdy, Jessica Spires, Viera Lukáčová, Ming‐Liang Tan, Andrew Babiskin, Xiaoming Xu, Liang Zhao, Michael B. Bolger
Abstract
PURPOSE: can be used to characterize ocular drug pharmacokinetic performance in rabbits for ointment formulations. METHODS: A newly OCAT™ model developed for fluorometholone, as well as a previously verified model for dexamethasone, were used to characterize the aqueous humor (AH) concentration following the administration of multiple ointment formulations to rabbit. The model uses the following parameters: application surface area (SA), a fitted application time, and the fitted Higuchi release constant to characterize the rate of passage of the active pharmaceutical ingredient from the ointment formulations into the tears in vivo. RESULTS: Parameter sensitivity analysis was performed to understand the impact of ointment formulation changes on ocular exposure. While application time was found to have a significant impact on the time of maximal concentration in AH, both the application SA and the Higuchi release constant significantly influenced both the maximum concentration and the ocular exposure. CONCLUSIONS: This initial model for ointment ophthalmic formulations is a first step to better understand the interplay between physiological factors and ophthalmic formulation physicochemical properties and their impact on in vivo ocular drug pharmacokinetic performance in rabbits.