Random sampling or 'random' model in skin flux measurements? [Commentary on "Investigation of the mechanism of flux across human skin in vitro by quantitative structure-permeability relationships"]

Transdermal therapy receives increasing attention as an attractive alternat ive to traditional drug delivery. Unfortunately the exact algorithm of tran sdermal permeation that could guide medicinal chemists towards delivery opt imization at an early stage of the drug design process still remains to be decoded. This paper discusses some major hurdles on the way to full underst anding of Quantitative Structure-Activity Relationships (QSAR) of skin perm eation. From the statistical perspective, a recently published combined dat a set is found to be inappropriate with respect to the distribution of majo r molecular descriptors, and therefore should be approached cautiously as a source for QSAR model training and in modelling of occupational and enviro nmental skin exposures. Published by Elsevier Science B.V.