Clinical Ocular Exposure Extrapolation Using PBPK Modeling and Simulation: Gatifloxacin Solution Case Study

Conference: AAPS
Software: GastroPlus®
Division: Simulations Plus
Therapeutic Areas: Oncology, Ophthalmology


  • Development of generic ophthalmic drugs has been extremely challenging due to the complexity of the ocular system and a lack of sensitive testing tools to evaluate its interplay with ophthalmic formulations.
  • Identifying the impact of formulation, manufacturing, and physicochemical properties between a generic ocular drug product and its reference listed drug product is critical to maintain safety and efficacy.
  • Conducting comparative clinical endpoint bioequivalence (BE) studies for generic ocular drug products is a significant challenge to pharmaceutical industry due to their associated cost and poor sensitivity.
  • FDA  is supporting ongoing efforts for the development of generic ophthalmic drug products and the enhancement of ocular PBPK modeling to support alternative BE approaches.
  • The purpose of this research is to demonstrate the value of ocular mechanistic absorption models linked to physiologically based pharmacokinetic (PBPK) models validated against rabbit pharmacokinetic (PK) data to predict clinical ocular exposure.
  • Enhancement of PBPK modeling is crucial in supporting an alternative BE approach where rabbits are the preferred animal species for PBPK-based extrapolation to predict exposure in human ocular tissue due to the physiological similarities between the rabbit and human eyeballs.

By Farah Al QaraghuliMing-Liang Tan, Ross Walenga, Andrew Babiskin, Liang Zhao, Viera Lukacova and Maxime Le Merdy

Presented at American Association of Pharmaceutical Scientists (AAPS) Pharm Sci 360 Boston, Massachusetts October 16-19, 2022​