The hairless rat: a relevant animal model to predict in vivo percutaneous absorption in humans?

Percutaneous absorption of 4 radiolabeled molecules was compared in the hairless rat (back) and in different anatomic sites in human (arm, abdomen, postauricular, forehead). The conditions under which these 4 compounds were administered (area treated, dose, vehicle, contact time, etc.) were similar in both species. The results showed that, in humans and rats, there exists the same rank order in total absorption: benzoic acid sodium salt less than caffeine less than benzoic acid less than acetylsalicylic acid. In both species there was a factor of 3 between the most and the least absorbed molecule. Although skin permeability varied significantly with the physicochemical nature of the compound administered, it also depended on the anatomic site involved. Independent of the molecule studied, the rank order of permeability of the sites tested in humans appeared as follows: arm less than or equal to abdomen less than postauricular less than forehead. There was a factor of 3 between the most and the least permeable sites. For each molecule and each anatomic site, the ratios of total percutaneous absorption human/hairless rat (back) were determined. For a given anatomic site and whatever the molecule tested, these ratios were constant. It thus appears that when conditions are carefully controlled, it may be possible, by measurements on animals, to predict the absorption of a compound in humans. Further experimentation with chemicals of varied physicochemical properties will be required for validation of the model.