Percutaneous absorption of 17 beta-estradiol in ovariectomized rhesus monkeys: skin and serum pharmacokinetics.

The skin and serum kinetics of percutaneous estradiol (E2) gel (Oestrogel; Besins-Iscovesco Laboratories, Paris, France) absorption in 11 ovariectomized rhesus monkeys (3 pretreated with diethylstilbestrol [DES]) was studied. The gel (1.5 mg E2) mixed with 7.5 x 10(5) cpm tritiated E2 (3H-E2) was applied to abdominal skin. Serial skin biopsies were taken from the application area and at 1 and 3 cm beyond, as well as from perineum and dorsal skin; and radioactivity measured to estimate tissue levels of E2 derived from percutaneous delivery. Simultaneous femoral serum samples were taken for RIA of E2. Skin 3H-E2 reached a peak at approximately 60 minutes, which was sustained for about 10 hours. Lateral diffusion of the radiolabeled E2 was limited to about 1 cm. Serum E2 levels reached a peak at 60 minutes and remained elevated for 20 hours after a single application. A strong correlation existed between skin and serum E2 levels: r = 0.828. DES did not modify the E2 skin absorption kinetics, but in 2 of 3 monkeys DES reduced the E2 serum levels, suggesting an effect after skin absorption. We conclude that percutaneously delivered E2 manifests a sustained entry into serum. The steady state of continuous release of E2 into circulation derives from a postabsorption skin reservoir of estrogen product.