Oral administration of griseofulvin, an important antifungal agent, has sometimes led to an undesired accompanying photosensitivity of the skin or eyelids. To determine the mechanism of this in vivo photosensitivity the photochemical reactivity of griseofulvin has been examined. Solutions of griseofulvin were photoreactive under all conditions (in methanol, methanol/water, acetonitrile, isopropyl alcohol, or PBS). The principal photoreaction was dechlorination when irradiation involved UV-A. With shorter wavelengths of irradiation the principle products arose from ring fragmentation, probably via an acyl fission (Norrish Type I) mechanism in addition to the photodechlorination. Under all conditions a small amount of isomerization was observed. The presence of oxygen slightly lowered the reaction rate, but otherwise had little effect on product distribution. Griseofulvin-sensitized formation of singlet oxygen was confirmed by the RNO assay and the increased rate of bleaching in D2O. It is possible that the in vivo photobiological damage caused by griseofulvin may be due both to the formation of reactive intermediates, particularly free radicals and the formation of singlet oxygen.
Buy this Article