Modeling percutaneous absorption for successful drug discovery and development.

From a drug discovery perspective, many factors can determine the percutaneous absorption of an active solute. Current in silico models are limited by their dependence on data generated from the permeation of solutes across normal human skin from aqueous solutions. In practice, the choice of formulation, the pertinent skin physiology, and the solute properties, including its clearance, potency, and enhancement, also define dermal delivery. Consequently, there is an emerging trend of using in silico methods to inform effective drug design and development that are based on a combination of QSAR/QSPR with physiologically based pharmacokinetic and pharmacodynamic (PBPKPD) models.