Cotransport of estradiol and ethanol through human skin in vitro: understanding the permeant/enhancer flux relationship.
The thermodynamic and kinetic limits of ethanol-enhanced estradiol skin transport have been investigated by studying the relationship between estradiol and ethanol steady-state flux in the cotransport of permeant and enhancer in situations in which there exists an enhancer solvent gradient across the skin ("asymmetric" configuration). For aqueous ethanol solution saturated with estradiol, the flux of estradiol across the human epidermal membrane is empirically observed to be linear with the ethanol flux. A physical model approach has been used to determine the basis of this empirical linearity and to predict permeant/enhancer transport across the skin for the asymmetric configuration. Enhancement factors, determined with a balanced ethanol concentration across the skin ("symmetric" configurations), are used to predict fluxes in the asymmetric configurations. The model demonstrates that ethanol enhances the stratum corneum transport of estradiol and of itself by increasing the respective diffusion coefficients at lower concentrations (less than 50%) and by both increasing the diffusion coefficients and decreasing the membrane activity coefficients at moderate concentrations (50 to 75%). The model also demonstrates that the permeant flux, in general, is not linear with the cotransported enhancer flux.
Liu
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Pharmaceuticals Division, CIBA-GEIGY Corporation, Ardsley, New York 10502.
Kurihara-Bergstrom
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Good
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D001693:Biological Transport, Active / Q000187:drug effects; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D004958:Estradiol / Q000493:pharmacokinetics*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D010539:Permeability; D012869:Skin Absorption / Q000187:drug effects*; D013268:Stimulation, Chemical; D013816:Thermodynamics
D000431:Ethanol; D004958:Estradiol