Photoallergenicity of a fluoroquinolone antibacterial agent with a fluorine substituent at the 8-position in guinea pigs exposed to long-wavelength UV light.
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.
Marutani
K
K
Toxicology Laboratory, Chugai Pharmaceutical Co. Ltd., Gotemba-Shi, Shizuoka, Japan.marutanikys@gt.chugai-pharm.co.jp
Otabe
Y
Y
Nagamuta
M
M
Matsubara
S
S
Otani
H
H
D000818:Animals; D000890:Anti-Infective Agents / Q000276:immunology / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D024841:Fluoroquinolones; D006168:Guinea Pigs; D006241:Haptens; D066298:In Vitro Techniques; D010787:Photosensitivity Disorders / Q000139:chemically induced* / Q000473:pathology*; D012867:Skin / Q000187:drug effects / Q000528:radiation effects*; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D006241:Haptens; D012996:Solutions; C077155:balofloxacin