INFLUENCE OF SKIN IRRITANTS ON PERCUTANEOUS-ABSORPTION

The effects of the application of skin irritants on the in vitro percu taneous absorption of three model compounds of diverse physicochemical properties, caffeine, indomethacin, and hydrocortisone, were investig ated. Norephedrine and imipramine, basic drugs with a known skin irrit ation potential, were employed to damage the skin. Treatment with nore phedrine increased the permeation of caffeine and hydrocortisone by tw o- to fourfold, while absorption of indomethacin declined an order of magnitude. A similar result was obtained for the effect of treatment w ith imipramine on transport of caffeine. Pretreatment with imipramine promoted hydrocortisone absorption 10-fold but, unlike norephedrine, d id not alter indomethacin permeation. While both treatments in vivo ca used an increase (norephedrine > imipramine) in the pH on the surface of skin and after tape-stripping the skin, only norephedrine caused ch anges in transepidermal water loss in vivo in man. Since imipramine wa s the more severe irritant as judged by erythema, alterations by irrit ants of barrier function appeared rather complex.