Development of an Ocular PBPK-PD model to predict drug-mediated intraocular pressure reduction in preclinical species

Authors: Le Merdy M, AlQaraghuli F, Lukacova V
Conference: ACoP
Keywords: ACoP2023, ocular, ophthalmic drug products, PBPK modeling, pharmacodynamics (PD)
Software: GastroPlus®
Division: Simulations Plus
Therapeutic Areas: Ophthalmology

Purpose

  • Glaucoma, caused by an elevation of the intra-ocular pressure (IOP), leads to vision loss
  • Modification of the aqueous humor (AH) dynamic using drugs can slow or prevent vision loss
  • Development of new or generic ophthalmic drug products designed to reduce IOP is based on preclinical pharmacokinetic (PK) & pharmacodynamic (PD) studies
  • Rabbits are the typical preclinical model to study drugs’ ocular PK but may not be sensitive to a drug (depending on drug’s mechanism of action), limiting pharmacodynamic (PD) clinical extrapolation
  • An alternative methodology to scale both PK and PD of ophthalmic drug products across multiple species is mandatory to support new and generic ophthalmic drugs development
  • The purpose of this study is to demonstrate the utility of an ocular PBPK (O-PBPK) model to describe drug mediated IOP reduction in preclinical species

By Maxime Le Merdy, Farah AlQaraghuli, Viera Lukacova

ACoP 14 American Conference on Pharmacometrics, National Harbor, MD, November 5th – 8th, 2023