Über die cutane Penetration von Sexualsteroidhormonen

Summary

Systematic pharmacokinetic tests were conducted in the skin of guinea pigs and hairless mice by topical application of radioactively labeled ethinyl estradiol, testosterone, progesterone, norethisterone acetate, d-norgestrel, and 17α-hydroxyprogesterone capronate. The animal tests were complemented by investigations in human skin.

Animal testing was carried out in vivo and in isolated skin. Testing in humans was done in clinically normal skin, “stripped” skin, and skin biopsies.

Quantitative determinations in the individual skin layers or media were complemented by qualitative microautoradiographs. The active ingredients had been incorporated each time in a water/oil emulsion, an oil/water emulsion, and a fatty base, particle size and concentration being the same. For each steroid hormone investigated, the penetration characteristics were demonstrated as a function of time. In some cases, the route of penetration was shown and the extent of penetration described as a function of formulation.

Active ingredient release was vehicle-dependent in both species and the sequence identical. About ten times as much ethinyl estradiol and testosterone penetrated the skin from the fatty base as the oil/water emulsion. The rate of penetration of the progestational steroid hormones was highest from oil/water emulsions. Distribution in the skin, which is also vehicle-dependent, is stated in addition to the penetrated portion.

In humans, penetration of clinically normal skin and skin from which the stratum corneum had been removed was compared and described. It was shown that with a change of skin condition the active ingredients, having their own time-related penetration characteristics, penetrate quickly from the contact surface, but that transport from the deeper layers of the dermis does not take place at the same time.