Advancing Physiologically Based Pharmacokinetic (PBPK) Modeling for Dermal and Ocular Drug Development

Sponsored By 

Chalk Talk Presenter(s)

• 

  Bryan Holland, PhD

  Senior Research Scientist
  Certara
  Sheffield, England, United Kingdom
• 

  Daniel Paterson, PhD (he/him/his)

  Research Scientist II
  Certara
  Sheffield, England, United Kingdom

Description: Physiologically based pharmacokinetic (PBPK) modeling provides a mechanistic framework to address key questions throughout drug development while reducing reliance on extensive in vivo or even animal studies. PBPK modeling is particularly valuable for dermal and ocular delivery routes of administration. These applications involve unique physiological barriers, exposure considerations, and complex formulation-dependent processes that benefit from a mechanistic approach.

This presentation highlights two PBPK models:

1. A mechanistic dermal absorption model that enables a bottom-up approach for dermal absorption to predict local and systemic compound exposures. The model supports in vitro in vivo extrapolation (IVIVE), informs experimental design, and incorporates dynamic re-parameterization of formulation characteristics to capture metamorphic processes critical for topical products.

2. A mechanistic ocular model developed to addresses challenges in predicting drug disposition in the eye, where diseases such as glaucoma and macular degeneration, as well as off-target toxic effects of systemic therapeutics, demand precise assessment of exposure within the different parts of the eye. To simulate the particular complexities of the eye, the model integrates finite element methods, anterior chamber convection, melanin binding, and intravitreal injection geometries. Here we provide verification studies against rabbit and human data for topical, intravitreal, oral, and IV administration routes that demonstrate its utility in supporting ocular drug development.