The in vivo fate of topically applied dithranol in the skin of the hairless rat. A comparison of continuous and short contact application.

The fate in vivo of topically applied 1,8-dihydroxy-9-anthrone (dithranol, anthralin) was investigated in the skin of the hairless rat, using a specially designed drug delivery system (film). The film was applied on intact skin as well as on skin with an impaired barrier function (stripped skin). The distribution of the drug was examined either after continuous application or at selected times after short contact periods. The exposed skin was extracted with diisopropylether and free dithranol, its dimer and quinone assayed by quantitative HPLC analysis. The incorporation of trace amounts of 3H-dithranol and 14C-dithranol in the vehicle made it possible to quantify the fraction of penetrated drug which was insoluble in ether. With continuous application to intact skin (up to 24 h), extractable dithranol rapidly reached a plateau level (15 min) and was concentrated in the stratum corneum. Substantial dimer formation occurred in both normal and stripped skin. Ether insoluble material rapidly predominated over soluble material, especially when the stratum corneum was absent. However, on short contact application (0.5-1 h), ether soluble material (dithranol in the stratum corneum) was quantitatively predominant in the intact skin. Removal of the vehicle after a short contact time resulted in the disappearance of dithranol from the skin (normal and stripped). In intact skin, the drug was converted into ether insoluble material. In the stripped skin, this insoluble fraction remained constant over the duration of the experiment (24 h).