title: Dermal absorption and metabolism of the antipsoriatic drug dithranol triacetate.
abstract: 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.
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000873:Anthracenes / Q000378:metabolism*; D000875:Anthralin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D001711:Biotransformation; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D051381:Rats; D012867:Skin / Q000201:enzymology; D012869:Skin Absorption
chemical_list: D000873:Anthracenes; C003629:triacetyldithranol; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D000875:Anthralin