ASSESSING THE INFLUENCE OF ETHANOL ON SIMULTANEOUS DIFFUSION AND METABOLISM OF BETA-ESTRADIOL IN HAIRLESS MOUSE SKIN FOR THE ASYMMETRIC SITUATION INVITRO

A novel theoretical model/method has been developed to predict permanent transport across skin for the 'asymmetric' case, i.e., for situations in which there is significant cotransport of an enhancer solvent along with the principal permeant. The method has successfully predicted effects of the simultaneous transport of ethanol on the simultaneous diffusion and metabolism of beta-estradiol (E2-beta) at steady state in hairless mouse skin using parameter values deduced from experiments conducted under symmetric conditions (i.e., the same ethanol concentration on both sides of the skin membrane). The studies have involved the determination of (a) effective ethanol concentration gradients and (b) skin position-dependent permeability coefficients and partition coefficients, concentration (activity) gradients, and fluxes for E2-beta and its transdermal metabolite, estrone (E1), with stripped skin and with full thickness skin. As this approach is quite general and as the asymmetric situation is the practical situation in vivo, it is believed that the outcomes of this study are important in transdermal/ dermal formulations research.