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.
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Authors | W Wiegrebe, A Retzow, E Plumier, N Ersoy, A Garbe, H P Faro, R Kunert |
Journal | Arzneimittel-Forschung
(Arzneimittelforschung)
Vol. 34
Issue 1
Pg. 48-51
( 1984)
ISSN: 0004-4172 [Print] Germany |
PMID | 6538420
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anthracenes
- triacetyldithranol
- Carboxylic Ester Hydrolases
- arylesterase
- Anthralin
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Topics |
- Administration, Oral
- Administration, Topical
- Animals
- Anthracenes
(metabolism)
- Anthralin
(administration & dosage, analogs & derivatives, metabolism)
- Biotransformation
- Carboxylic Ester Hydrolases
(metabolism)
- Injections, Intravenous
- Male
- Mice
- Rats
- Skin
(enzymology)
- Skin Absorption
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