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

Authors: Le Merdy M, Zheng Y, Lukacova V, Tan ML, Babiskin A, Zhao L
Conference: AAPS
Keywords: levofloxacin, ophthalmic drug products, PBPK models, rabbit pharmacokinetic (PK) data
Software: GastroPlus®
Division: Simulations Plus
Therapeutic Areas: Ophthalmology

Purpose​

  • Development of generic ophthalmic drug products is 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 any differences in manufacturing, formulation, or physicochemical characteristics between a generic ocular drug product and its reference listed product is critical to maintain safety and efficacy for patients ​
  • Due to their poor sensitivity, associated costs, and ethical limitations, comparative clinical endpoint bioequivalence (BE) studies for a generic ocular drug product are a significant challenge to pharmaceutical industry and a burden for generic development​
  • The purpose of this research is to demonstrate the value of ocular mechanistic absorption models (MAM) linked to physiologically based pharmacokinetic (PBPK) models validated against rabbit pharmacokinetic (PK) data to predict clinical ocular exposure

By Maxime Le Merdy, Yujuan Zheng, Viera Lukacova, Ming-Liang Tan, Andrew Babiskin and Liang Zhao

​Presented at American Association of Pharmaceutical Scientists (AAPS) PharmSci 360, October 17-20, 2021