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Title: Reduced phototoxicity of a fluoroquinolone antibacterial agent with a methoxy group at the 8 position in mice irradiated with long-wavelength UV light. Author: Marutani K, Matsumoto M, Otabe Y, Nagamuta M, Tanaka K, Miyoshi A, Hasegawa T, Nagano H, Matsubara S, Kamide R. Journal: Antimicrob Agents Chemother; 1993 Oct; 37(10):2217-23. PubMed ID: 8257147. Abstract: A newly developed fluoroquinoline, Q-35 (8-OCH3), in which a methoxy group was substituted at the 8 position of the quinoline nucleus, was very stable under irradiation with long-wave UV light (UVA). Derivatives, a fluoroquinolone with no substitution (the 8-H analog) and one in which a fluorine was substituted (the 8-F analog), were degraded in their solutions by the UVA irradiation. The phototoxic inducibility by these 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 lesions 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 were also observed microscopically in groups receiving the 8-H or 8-F analog but not in groups receiving Q-35 (8-OCH3). Similar inflammatory reactions were observed to occur in a dose-dependent manner with other available fluoroquinolone antibacterial agents such as lomefloxacin, enoxacin, norfloxacin, ciprofloxacin and ofloxacin. These results suggest that the introduction of a methoxy group at the 8 position of the quinolone nucleus is important for the reduction of phototoxicity.[Abstract] [Full Text] [Related] [New Search]