Photochemistry and Phototoxicity of Fluocinolone 16,17-Acetonide

Fluocinolone 16,17-acetonide is a corticosteroid used topically
to treat various inflammatory skin diseases. Its photoreactivity
was studied under UV-A and UV-B light in aqueous buffer in
the presence of oxygen. This drug is photolabile under UV-B
light and, to a lesser extent, under UV-A light, which is absorbed
far less. In phosphate buffer, approximately 80% of fluocinolone
acetonide decomposes after 5 J/cm2 of UV-B irradiation,
whereas under 30 J/cm2 of UV-A light approximately only 20%
decomposes. Both the drug and its photoproducts have been
evaluated through a battery of in vitro studies and found to
cause photohemolysis and induce photodamage to proteins
(erythrocyte ghosts, bovine serum albumin) and linoleic acid.
In addition, one of the photoproducts (the 17-hydroperoxy
derivative) is highly toxic in the dark. Therefore, both loss of
therapeutic activity and light-induced adverse effects may be
expected when patients expose themselves to sunlight after drug
administration. A major mechanism for phototoxicity involves
radicals forming from drug breakdown, at least under UV-B,
although reactive oxygen species may play a role, particularly
under UV-A.