The effect of structural QSAR parameters on skin penetration

The permeability coefficients (log kp) of solutes through stratum corneum have been previously related to the octanol-water partition coefficients (log Poct) and solvatochromic parameters. In this study, permeation coefficient data are related to the theoretical chemistry-derived structural parameters and also molecular connectivity and molecular shape indices. The results show that these parameters are comparable with the solvatochromic parameters in correlation with log kp. Log Poct can be corrected by the theoretical parameters to explain permeation coefficients and the equilibrium distribution of compounds between the stratum corneum and water (log Km). Diffusion estimated from the expression log(D/h) = log kp-log Km, where D is the diffusion coefficient and h is the path length for diffusion was also analyzed successfully by the structural parameters.