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

Authors: Lukacova V, Tan ML, Babiskin A, Zhao L, Le Merdy M
Conference: ARVO
Keywords: mechanistic absorption models (MAM), moxifloxacin, ocular, PBPK modeling, pharmacokinetic (PK) data
Software: GastroPlus®
Division: Simulations Plus

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 drug 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
  • 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, Viera Lukacova, Ming-Liang Tan, Andrew Babiskin and Liang Zhao

Presented at ARVO 2022 Annual Meeting, May 1-4, 2022, Denver, Colorado