Quantitative evaluation of ethanol effects on diffusion and metabolism of beta-estradiol in hairless mouse skin.
The influence of low levels of ethanol on the simultaneous diffusion and metabolism of beta-estradiol (E2 beta) in hairless mouse skin was quantitatively evaluated. A wide range of diffusion/metabolism experiments was conducted with full-thickness skin, stripped skin, and dermis at the various ethanol levels. The experiments were carried out in a two-chamber diffusion-cell system where ethanol was present in both the donor and the receiver chambers at equal concentrations. Analysis of the experimental data with several enzyme distribution models further showed that the best model was that for which the enzyme activity resided totally in the epidermis and near the basal layer of the epidermis. The ethanol effects were separated and quantified in terms of the diffusion and metabolism parameters. Aqueous ethanol, even at low concentrations (greater than or equal to 25%), was found to have two important effects on E2 beta transport: ethanol functions as an inhibitor of the enzymatic conversion of E2 beta to estrone (E1) in the viable epidermis, and ethanol is able to enhance the transport of permeants across the lipoidal pathway of the stratum corneum.
Liu
P
P
Department of Pharmaceutics, University of Utah, Salt Lake City 84112.
Higuchi
W I
WI
Song
W Q
WQ
Kurihara-Bergstrom
T
T
Good
W R
WR
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D004958:Estradiol / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D004970:Estrone / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008812:Mice, Hairless; D008954:Models, Biological; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*
D004970:Estrone; D000431:Ethanol; D004958:Estradiol