QUANTITATION OF SIMULTANEOUS DIFFUSION AND METABOLISM OF BETA-ESTRADIOL IN HAIRLESS MOUSE SKIN - ENZYME DISTRIBUTION AND INTRINSIC DIFFUSION METABOLISM PARAMETERS

This paper describes a systematic experimental and theoretical study of the simultaneous diffusion and metabolism of β-estradiol (E2β) in hairless mouse skin (in vitro). The strategy involved (a) considering a general three-layer skin model (stratum corneum, epidermis, and dermis), (b) considering three possible enzyme distributions (Model A: homogeneous enzyme distribution across both epidermis and dermis; Model B: homogeneous enzyme distribution in the epidermis; and Model C: homogeneous enzyme distribution in the 'basal cell layer' only of the epidermis), and (c) carrying out a wide range of independent diffusion experiments so that a 'best' model may be deduced in which all of the experimental data are consistent with the model and a single set of transport and metabolism parameters. The various diffusion/metabolism experiments included using three skin membranes (dermis, stripped skin, and full-thickness skin), two membrane configurations (transport of permeants in the direction: stratum corneum → epidermis → dermis, and in the reverse direction), two permeants (E2β and estrone, E1, the principal metabolite), and measuring three fluxes (forward fluxes of E2β and E1 and the back flux of E1). Analysis of all of the experimental data demonstrated that Model C was superior to Models B and A; within the uncertainties of the experiments and model fitting, Model C agreed well with the data in all instances while the predictions of Models B and A exhibited significant deviations from the experimental data. © 1990.