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, sparfloxacin was intravenously administered once at 10, 30 or 100 mg/kg to female mice, followed immediately by ultraviolet-A irradiation for 4 h (21.6 J/cm2). The auricular thickness was measured 4, 24, 48, 72 and 96 h later, and then the histopathological examination of the auricle was performed. As results, the auricular thickness increased from 30 mg/kg, and edema, cellular infiltration, epidermal necrosis and focal loss of the auricle were also morphologically observed. On the basis of these information, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, lomefloxacin, norfloxacin and ofloxacin were given intravenously to mice at a fixed dose of 100 mg/kg to compare their potential phototoxicities. Certain quinolones caused the auricular lesions in the following rank order (no to severe change): vehicle control (no-phototoxicity) = gatifloxacin = ofloxacin < ciprofloxacin = norfloxacin < enoxacin = fleroxacin < lomefloxacin = sparfloxacin. From the view point of the structure-phototoxicity relationship, quinolones possessing a fluorine, nitrogen or hydrogen at the 8 position of the quinolone ring evoked phototoxicity in the mouse auricle. These results demonstrate that phototoxicity induced by quinolones would be related to the property of a substituent at the 8 position of the quinolone ring.
