ABSTRACT
This chapter describes physiologically based pharmacokinetic models, their use as a tool to quantify and understand the process of dermal penetration, and their suitability for dose, route, and species extrapolation. One of the big advantages of dermal physiologically based pharmacokinetic (PB-PK) models over traditional in vivo methods is the ability to accurately describe nonlinear biochemical and physical processes. The building block of a PB-PK model is the compartment. A compartment is a collection of fluids or tissues and/or organs that are grouped together because of similar physiological and pharmacokinetic characteristics rather than anatomical considerations. As knowledge is gained in the laboratory, each new understanding should be quantitatively described in the model. Species-specific physiological parameters, that is, blood flow and volumes of organs, are often available in the physiology handbooks or reviews or from published PB-PK models. PB-PK modeling can be applied to the effect of vehicles on penetration rates and penetration enhancement by understanding and quantitating the processes involved.
