Wiegrebe W, Retzow A, Plumier E, Ersoy N, Garbe A, Faro H P, Kunert R
Arzneimittelforschung. 1984;34(1):48-51.
Percutaneous absorption, excretion kinetics, and metabolism of dithranol triacetate (2) have been investigated in Wistar rats. By the use of two differently labelled molecules--3H in the anthracene nucleus and 14C in the acetoxy groups of 2, resp.--the fate of the different parts of the dithranol triacetate molecule could be followed. After injection, large amounts of 2 are cleaved under the influence of enzymes into acetate and dithranol. These deacetylated metabolites lose half their 3H label with formation of 3H2O. In urine, 1,8-diacetoxy-9-anthrone, 1-acetoxy-8-hydroxy-9-anthrone, 1,8-dihydroxy-9,10-anthraquinone and its diacetate were found as metabolites. After dermal application, unchanged 2 is practically not absorbed at all. Arylesterases which, according to in vitro studies, are present in or on the skin, hydrolyse dithranol triacetate to give free dithranol. Up to 33% of the latter are absorbed from under an occlusive dressing. Dithranol triacetate, therefore, shows pro-drug characteristics for the treatment of psoriasis.
在Wistar大鼠中研究了三醋酸地蒽酚（2）的经皮吸收、排泄动力学和代谢。通过使用两种不同标记的分子——蒽核中的3H和2的乙酰氧基中的14C——可以追踪三醋酸地蒽酚分子不同部分的去向。注射后，大量的2在酶的作用下裂解为醋酸盐和地蒽酚。这些脱乙酰代谢物在形成3H2O时失去一半的3H标记。在尿液中，发现1,8 - 二乙酰氧基 - 9 - 蒽酮、1 - 乙酰氧基 - 8 - 羟基 - 9 - 蒽酮、1,8 - 二羟基 - 9,10 - 蒽醌及其二醋酸酯作为代谢物。经皮肤应用后，未变化的2几乎完全不被吸收。根据体外研究，皮肤中或皮肤表面存在的芳基酯酶将三醋酸地蒽酚水解为游离的地蒽酚。在封闭敷料下，高达33%的后者被吸收。因此，三醋酸地蒽酚显示出用于治疗银屑病的前药特性。
