ABSTRACT
Owing to the increase in the availability of computer hardware and software over the last three decades, methods that are based on physiological and pharmacokinetic principles are now feasible alternatives for analysis of in vivo skin penetration. These physiologically based pharmacokinetic (PB-PK) approaches mathematically describe the dynamics of chemicals in the body in terms of rates of blood fl ow, permeability of membranes, and partitioning of chemicals into tissues. Characterizing absorption in terms of parameters, which are measurable and species specifi c, facilitates extrapolations to the real species of interest, providing these parameters are known or can be determined for humans. This chapter describes PB-PK models, their use as a tool to quantify and understand the process of dermal absorption and penetration, and their suitability for dose, route, and species extrapolation.
