Photoallergenicity of a Fluoroquinolone Antibacterial Agent with a Fluorine Substituent at the 8-Position in Guinea Pigs Exposed to Long-Wavelength UV Light

Abstract

The 8-position of the quinolone ring of balofloxacin (BLFX), one of fluoroquinolones, was replaced with fluorine to obtain the 8-F. When an aqueous solution of bovine serum albumin (BSA) containing the 8-F was exposed to long-wavelength UV light (UVA) at a rate of 2.5 J/cm², the absorbance of BSA at 300 nm or longer wavelengths increased markedly in comparison to that of native BSA. In addition, when a homogenate of skin tissue from Hartley guinea pigs was exposed to UVA (2.5 J/cm²) in the presence of the 8-F and then injected subcutaneously into guinea pigs, the animals produced IgG class antibody specific to the 8-F and its UVA-irradiation product. No such phenomenon, however, was observed when the parent compound, i.e., BLFX which possesses a methoxy group at the 8-position, was used instead of the 8-F. In a subsequent experiment, the 8-F was administered either orally or topically to the shaved neck of guinea pigs and then irradiated with UVA (5 J/cm²) once daily for 5 days. When the treated animals were challenged by a combination of UVA irradiation (5 J/cm²) and either an oral or intradermal administration of the 8-F, 2 and 3 of the 5 animals showed redness and erythema on the irradiated area, respectively. However, no change was observed when BLFX was used instead of the 8-F. These results suggest that the introduction of a fluorine substituent to the 8-position of quinoline ring of fluoroquinolones induces photoallergic responses in which the fluoroquinolone or its photo-denatured product(s) act as an allergen.