Clinical Ocular Exposure Extrapolation for Ophthalmic Solutions Using PBPK Modeling and Simulation

• DOI: 10.1007/s11095-022-03390-z
• Publication Date: 2022-09-23T20:19:28Z
• Authors: Maxime Le Merdy; Farah AlQaraghuli; Ming-Liang Tan; Ross Walenga; Andrew Babiskin; Liang Zhao; Viera Lukacova
• Keywords: Gatifloxacin

Abstract Background The development of generic ophthalmic drug products is challenging due to the complexity ocular system, and a lack sensitive testing evaluate interplay physiology with formulations. While measurements concentration at site action in humans are typically sparse, these more easily obtained rabbits. purpose this study demonstrate utility an physiologically based pharmacokinetic (PBPK) model for translation exposure from rabbit human. Method Ocular Compartmental Absorption Transit (OCAT™) within GastroPlus® v9.8.2 was used build PBPK models levofloxacin (Lev), moxifloxacin (Mox), gatifloxacin (Gat) solutions. eye. were subsequently predict Lev, Mox, Gat after solution administrations humans. Drug-specific parameters as fitted validated OCAT model. physiological scaled match human physiology. Results simulations well described observed concentrations eye compartments following different doses various administration schedules. clinical solutions schedules predicted. Conclusion Even though additional case studies types active pharmaceutical ingredients (APIs) formulations will be needed, current represents important step validation extrapolation method using models.