Percutaneous absorption of 17β-estradiol in ovariectomized rhesus monkeys: skin and serum pharmacokinetics *

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