Further light is shed on topical therapy.

Abstract

Under in vitro conditions that mimic use of the drug in its pharmaceutical vehicle, Lebwohl and coauthors (p. 594) describe extensive degradation induced by ultra-violet light on the Vitamin D derivative calcitriol (Lebwohl et al, 2003). Not only was the extent of degradation greater than 90%, but also it occurred in a period of 10 minutes. Control samples in ambient light were relatively stable. The authors also show that calcitriol is able to absorb UV radiation and eiectively reduce transmission of both UVA and UVB wavelengths. The discussion and conclusion of the authors strongly recommend that in choosing combination therapies of calcitriol and light for the treatment of psoriasis that the light be administered before application of the vitamin D derivative.This phenomenon has been reported previously with another vitamin D analog, calcipotriene (Lebwohl et al, 1997). Cursory inspection of the chemical structures of vitamin D based drugs (Fig 1a) reveals an array of conjugated double bonds that absorb in the UV with a l max 264 nm. It is not surprising, therefore, that when exposed to UV light such molecules absorb and can undergo chemical changes. The questions raised by this in vitro report are far-reaching, and the authors allude to the possibility that the degradation products generated by photo-transformation may possess pharmacologic activity. In the case of this highly potent Vitamin D3 derivative the quantity of active drug in each gram of ointment is only 3 micrograms; consequently it becomes a challenging task to determine if indeed tiny quantities of conversion products may be linked to pharmacological properties of the drug in the skin. Another lesson from this study is that direct exposure of vitamin D treated skin to sunlight should be avoided. The interaction of topically applied drugs with UV light is not uncommon since the presence of conjugated double bonds in drug actives lends them to have stability problems in the presence of UV light. Tretinoin, all trans retinoic acid, is another light sensitive molecule by nature of the array of conjugated double bonds (Fig 1b). In a study carried out with tretinoin applied to primate skin (Lehman et al, 1988), it was demonstrated that extensive conversion to 13 is-retinoic acid (iso tretinoin) was observed. The results prompted speculation about the role of iso tretinoin in