IVPT Data Heterogeneity – How to Make Sense out of It Using PBPK Model

Physiologically based pharmacokinetic (PBPK) modeling is gaining importance in drug development. Recently, the Multi-phase Multi-layer Mechanistic Dermal Absorption (MPML MechDermA) model for simulating topical application was published and subsequently repurposed for simulating in vitro permeation tests using pig ear skin. In previous studies, the model validation process was conducted with caffeine. The current work describes literature experimental data–based development and verification of PBPK model of testosterone permeation through human and pig ear skin under in vitro conditions using the Simcyp® simulator version 23 (Certara UK, Sheffield, UK). Additionally, the usefulness of the pig ear skin model in improving the accuracy of human skin-based permeability predictions was evaluated. A total of 2 pig skin and 5 human skin experiments found in the scientific literature were used for model evaluation. The optimisation process, based on data derived from pig skin experiments, enabled predictions of cumulative amount in receptor solution for the human model when the vehicle composition remained consistent. The analysis revealed the critical impact of accurate formulation characterisation on model performance.