Sparfloxacin phototoxicity: potential photoaugmentation by ultraviolet A and B sources

Sparfloxacin, a quinolone antibacterial agent, frequently elicits photosensitive skin reactions. Our clinical studies of patients treated with sparfloxacin have demonstrated that this photosensitivity is primarily phototoxic and that a marked erythematous response is induced by sequential irradiation with ultraviolet A (UVA) and B (UVB) but not UVA or UVB alone, suggesting potential synergism between UVA and UVB. We evaluated the phototoxicity of this agent using in vitro DNA breaking activity and in vivo murine cutaneous responses. Sparfloxacin induced DNA strand breaks in vitro and converted the supercoiled closed circular form of plasmid DNA to the open circular form by its photodynamic action. In mice, the topical application of sparfloxacin and subsequent irradiation with UVB, but not UVA, induced ear swelling responses. However, the UVB-induced ear swelling response was augmented by irradiation with UVA before or after UVB exposure. Such interaction between UVA and UVB in the production of ear swelling was further confirmed by systemic administration of sparfloxacin. Our study suggests that sparfloxacin is a unique phototoxic agent in that photosensitivity dermatitis is evoked by photoaugmentation between UVA and UVB.