MODELING IN-VIVO HUMAN SKIN ABSORPTION

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