Transport of beta-estradiol in freshly excised human skin in vitro: diffusion and metabolism in each skin layer.
This paper describes an experimental and theoretical evaluation of beta-estradiol (E2) transport in post-surgery fresh human skin in vitro. Necessary auxiliary experimental methods were newly developed for these studies. The experimental fluxes of E2 and the metabolite, estrone (E1), using the dermis, stripped skin, and split-thickness skin were consistent with a model considering the human skin as a three-layer (stratum corneum, viable epidermis, and dermis) membrane with the enzyme activity mainly residing in the basal layer of the viable epidermis. The diffusion and metabolism parameters for each skin layer were determined in the overall transdermal transport of E2. Compared to fresh hairless mouse skin, fresh human skin appears more resistant to the stratum corneum diffusion of E2 and is much less capable of metabolizing E2 to E1. These in vitro results have been extrapolated to the possible in vivo human skin situation with blood vessels directly beneath the viable epidermis providing "sink" conditions a short distance from the dermo-epidermal junction. The model analysis has demonstrated that there would be less metabolism and that a much smaller amount of the transdermal metabolite (E1) would be taken up by the blood capillary due to the shorter dermis path length for permeants in vivo than in the in vitro case using dermatomed split-thickness skin.
Liu
P
P
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City 84112.
Higuchi
W I
WI
Ghanem
A H
AH
Good
W R
WR
D001692:Biological Transport; D004058:Diffusion; D004958:Estradiol / Q000493:pharmacokinetics*; D006801:Humans; D012867:Skin / Q000378:metabolism*
D004958:Estradiol