Follicles play an important role in percutaneous absorption.

The relative importance of stratum corneum and follicles in percutaneous absorption is not fully understood. In order to quantitatively investigate the importance of the transappendageal route, we have previously developed a model of skin without follicles regrown dorsally on the hairless rat. Percutaneous absorption was compared, using a diffusion cell, in appendage-free skin relative to normal skin, and a predominant role of follicles for in vitro diffusion of [3H]hydrocortisone was noted. Results presented here of in vitro diffusion of tritiated hydrocortisone, niflumic acid, caffeine, and p-aminobenzoic acid, applied in acetone, confirm that appendageal diffusion is the major pathway in hairless rat skin. In the absence of follicles, the steady-state flux and the amounts diffusing in 24 or 48 h are 2-4 times lower than in normal skin. These results were confirmed in a second model in which diffusion of [3H]hydrocortisone was studied on skin samples taken one day after birth, at which time rat skin is still devoid of follicles, relative to five-day postnatal skin samples, in which follicles are fully developed. The steady-state flux and the total diffusion in 24 h were fivefold lower in follicle-free skin. These results support the view that follicles may have a far greater importance in percutaneous absorption than is generally assumed.