Modelling In Vivo Human Skin Absorption

We correlated skin absorption data, determined in vivo in man under different experimental conditions for a set of 28 diverse chemical compounds, with experimental permeation constants (KpF) obtained for 8 compounds in vitro on human skin, and with the calculated Kp (Kp QSAR) according to a modified Potts-Guy algorithm. Fick's first law of diffusion was applied to calculate in vivo penetration constants Kpmax at the point of maximum flux Jmax. The occlusion variable shows a positive coefficient linking the degree of occlusion to larger logJmax permeation rates. The most significant correlation is seen for a sub-set of 10 semi-occluded applications of different compounds, with an r = 0.83 for logKpmax vs. logKpQSAR, and a somewhat lower value r = 0.79 for logKpmax vs. logKpF. We could thus demonstrate that a pseudo-steady state presents a valid alternative to infinite-dose dermal absorption conditions or predicted permeation values, even though Fick's postulated steady state is not achieved and the maximum flux value, Jmax, is used instead.