PERCUTANEOUS PENETRATION OF DRUGS - A QUANTITATIVE STRUCTURE PERMEABILITY RELATIONSHIP STUDY

Human skin permeation data taken from the literature were analyzed for quantitative relationships with physicochemical properties and structural descriptors. No correlations exist with molecular weights and solvent-accessible surface areas. In most cases, skin permeation was inversely correlated with the parameter DELTA-log P(oct-hep) (i.e., log P(octanol) minus log P(heptane)), which is mainly a measure of the H-bond donor acidity of the solutes. Lipophilicity itself, as expressed by log P(octanol), also contributes positively to skin permeation in some cases. The results of this quantitative structure-permeability relationship study are interpreted in terms of a unified mechanistic model whereby drugs can permeate via an intercellular route (correlation with both DELTA-log P(oct-hep) and log P(oct)) and/or a transcellular route (correlation with log P(oct) only).