European Journal of Pharmaceutics and Biopharmaceutics 2002-09-01

Comparison of skin distribution of hydrolytic activity for bioconversion of beta-estradiol 17-acetate between man and several animals in vitro.

Tomohiro Hikima, Kayoko Yamada, Tohru Kimura, Howard I Maibach, Kakuji Tojo

Index: Eur. J. Pharm. Biopharm. 54(2) , 155-60, (2002)

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Abstract

We have investigated the distribution of hydrolytic enzymes which metabolize beta-estradiol 17-acetate (EA) to beta-estradiol (E) in man and animal skins in vitro. The distribution of hydrolytic enzymes in human cadaver, hairless dog, rat and hairless mouse skin, was investigated by a skin-slicing technique. We performed histological studies with hematoxylin and eosin stain. The highest amount of metabolite (E) appeared in the layers of 80-120 microm from the skin surface, the basement layer in human skin, while the amount of metabolite was distributed evenly in the hairless dog skin from 0 to 180 microm. In the rat and hairless mouse skin, on the other hand, peak levels of metabolite were observed in the basement layer of dermis, the surrounding area of the cutaneous plexus. The total metabolic activities in the area of epidermis in human, hairless dog and hairless mouse skin were 2.59, 8.03 and 0.33 x 10(-4) microg/ml/microm/h, respectively. The values in whole skin layers in the hairless dog and hairless mouse skin were 3.35 and 1.85 x 10(-4)microg/ml/microm/h, respectively. EA transported across the human and hairless dog skin can be effectively metabolized before entering the capillary. Among animal models investigated, hairless dog skin might be the most facile model in simulating drug metabolism for human skin under the clinical (in vivo) conditions. Hairless mouse skin, on the other hand, was also an excellent model in excised human skin under in vitro conditions.