Algorithms for skin permeability using hydrogen bond descriptors: the problem of steroids

Several algorithms that use hydrogen bond descriptors have been published for the permeation of compounds from aqueous solution through human stratum corneum. In the present work, all the skin permeability coefficients, Kp in cm s(-1), used in these algorithms for non-steroids have been correlated through the Abraham equation to give a new algorithm: log Kp = -5.241 + 0.437R(2) - 0.410 pi(2)(H) - 1.631 Sigma alpha(2)(H) - 3.286 Sigma beta(2)(H) + 2.012V(x) (1) (n = 47, r(2) = 0.9567, s.d. = 0.197, F = 181) where n is the number of solutes, r is the correlation coefficient, s.d. is the standard deviation, and F is the F-statistic. The solute descriptors are: R-2 and excess molar refraction, pi(2)(H) the dipolarity/polarizability, Sigma alpha(2)(H) and Sigma beta(2)(H) the overall or effective hydrogen-bond acidity and basicity, and V-x the McGowan characteristic volume. Equation 1 is a reasonably good predictor of log Kp values for steroids as given by Johnson et al, but not for those given by Scheuplein.