Structure–phototoxicity relationship in Balb/c mice treated with fluoroquinolone derivatives, followed by ultraviolet-A irradiation

Abstract: We examined the structure–phototoxicity relationship for fluoroquinolone antimicrobial agents (quinolones) using female albino Balb/c mice. First of all, to obtain an optimum dosage level for induction of phototoxicity, the prototype phototoxicant sparfloxacin was intravenously administered once at 10mg/kg, 30mg/kg or 100mg/kg to female mice, followed immediately by ultraviolet-A (UVA) irradiation for 4h (21.6J/cm2). The auricular thickness was measured at pre-dose (0h), 4, 24, 48, 72 and 96h post-dose, and then the histopathological examination of the auricle was performed. As results, the auricular thickness increased from 30mg/kg, in conjunction with edema, cellular infiltration, epidermal necrosis and focal loss of the auricle. On the basis of these information, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, lomefloxacin, norfloxacin and ofloxacin were given intravenously to mice at a fixed dose of 100mg/kg to compare their potential phototoxicities. Certain quinolones caused the auricular lesions in the following rank order (from lowest to highest): vehicle control (non-phototoxicity)=gatifloxacin=ofloxacin<ciprofloxacin=norfloxacin<enoxacin=fleroxacin<lomefloxacin=sparfloxacin. From the viewpoint of the structure–phototoxicity relationship, quinolones possessing the C-8 substituent with a fluorine or hydrogen and 1,8-naphthyridine derivative evoked phototoxicity in the mouse auricle. These results demonstrate that phototoxicity induced by quinolones would be related to the property of the eighth position. [Copyright &y& Elsevier]