REDUCED PHOTOTOXICITY OF A FLUOROQUINOLONE ANTIBACTERIAL AGENT WITH AMETHOXY GROUP AT THE 8-POSITION IN MICE IRRADIATED WITH LONG-WAVELENGTH UV-LIGHT

A newly developed fluoroquinoline, Q-35 (8-OCH3), in which a methoxy g roup was substituted at the 8 position of the quinoline nucleus, was v ery stable under irradiation with long-wave UV light (UVA). Derivative s, a fluoroquinolone with no substitution (the 8-H analog) and one in which a fluorine was substituted (the 8-F analog), were degraded in th eir solutions by the UVA irradiation. The phototoxic inducibility by t hese derivatives was further studied in a murine model. When mice were dosed orally with 800 mg of Q-35 (8-OCH3) per kg of body weight, the maximum dose given, and exposed to the UVA light, no inflammatory lesi ons were observed in their ears. Ear redness was marked in mice given more than 12.5 mg of the 8-F analog or 200 mg of the 8-H analog per kg . Histopathological changes, edema, and infiltration of neutrophils we re also observed microscopically in groups receiving the 8-H or 8-F an alog but not in groups receiving Q-35 (8-OCH3). Similar inflammatory r eactions were observed to occur in a dose-dependent manner with other available fluoroquinolone antibacterial agents such as lomefloxacin, e noxacin, norfloxacin, ciprofloxacin and ofloxacin. These results sugge st that the introduction of a methoxy group at the 8 position of the q uinolone nucleus is important for the reduction of phototoxicity.