Age-related changes in skin permeability of hydrophilic and lipophilic compounds in rats

The effect of age on intact and stripped skin permeability of lipophilic (k etoprofen and isosorbide dinitrate) and hydrophilic permeants (deuterium ox ide and diclofenac sodium) was investigated using STD: Wistar male rats age d 5 to 180 days. The permeability of permeants through intact skin increase d with increasing lipophilicity of the permeants at each age, indicating th at the permselective property of rat skin is revealed even at 5-days-old. T he permeability coefficients through intact skin decreased with increasing age, and the extent uf these decreases was higher for lipophilic pel permea nts than that fur hydrophilic permeants. On the other hand, the stripped sk in permeability of permeants was almost the same at each age, and with agin g each permeability coefficient through stripped skin decreased up to 71 da ys, dramatically during 21-90 days and then gradually again to 180 days. Th e thickness of the stratum corneum and stripped skin increased according tu age with faster growth during 21-90 days. The reciprocal of the mean thick ness of stratum corneum and stripped skin correlated well with intact skin and stripped skin permeability (r > 0.9), respectively. These results clari fied that the permselectivity of rat skin against lipophilicity of permeant exists at the latest from 5 days after birth. In addition, it is speculate d that the thickness of skin is a large factor in the decrease of its perme ability with age.