Glucocorticosteroids, natural hormones derived from \uf061-pregnane, are potent therapeutic agents for the treatment of a broad range of inflammatory diseases. Semisynthetic derivatives are widely used systemically mainly for the treatment of rheumatoid diseases and allergic manifestations, and many of them are effective by topical use in dermatoses and other skin diseases. This class of drugs is sensitive to UV radiation. They are a typical example of bichromophoric moiety: all possess an aliphatic ketone in the side chain linked to position 17 of the D ring, which absorbs UVB light. Ring A bears a keto group that is conjugated with either one or two double bonds, depending on the specific drug. In the former case (i.e., hydrocortisone) the chromophore is mainly sensitive to UVB. In the latter (i.e., betamethasone, fluocinolone, triamcinolone, flumethasone) both UVA and UVB effectively induce photolysis. The photodegradation of these drugs was studied in vitro (in the solid state, in organic and aqueous solutions, in commercial formulations) and ex vivo (in the pig skin). Both primary photoprocesses, cyclohexadienone \u2018lumi\u2019 rearrangement (under UV-A) and C-20 ketone homolysis (under UV-B) occur and the main photoproducts formed have been isolated and characterized. Any modification of the structure of corticosteroids, in particular the loss of the side-chain, has profound effect on their anti-inflammatory activity.
The drugs are also able to photoreact with biological substrates mainly through radical intermediates and one of them (betamethasone) shows phototoxic effects both ex vivo and in vivo (mice) too. All these results suggest to protect these drugs from light not only during storage but also after in vivo administration to avoid loss of therapeutic activity and potential phototoxic reactions
