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Toxicological Sciences 56, 290-296 (2000)
Copyright © 2000 by the Society of Toxicology

Possible Relationship between Phototoxicity and Photodegradation of Sitafloxacin, a Quinolone Antibacterial Agent, in the Auricular Skin of Albino Mice

Kohji Shimoda*,1, Toshiko Ikeda*, Satoshi Okawara* and Michiyuki Kato{dagger}

* Tokyo R&D Center, Daiichi Pharmaceutical Co., Ltd., 1–16–13 Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan; and {dagger} Drug Safety Administration Department, Daiichi Pharmaceutical Co., Ltd., 2–16–1, Kyobashi, Chuo-ku, Tokyo 104-8369, Japan

We compared the phototoxic potential of the quinolone antibacterial agent sitafloxacin with those of lomefloxacin and sparfloxacin. Female BALB/c mice were given a single intravenous administration of sitafloxacin, lomefloxacin, or sparfloxacin at 10 or 40 mg/kg, followed by ultraviolet-A (UVA) irradiation for 4 h (21.6 J/cm2). At 10 mg/kg, all quinolones induced either none or minimum inflammation in the auricle. At 40 mg/kg, sitafloxacin induced mild phototoxic inflammation in the dermal skin, while lomefloxacin and sparfloxacin induced very severe inflammation. In particular, 2/5 animals of the lomefloxacin group showed partial necrosis in the dermis and epidermis. We then determined the time course change of sitafloxacin concentrations in serum and auricular tissue by high performance liquid chromatography. Sitafloxacin concentrations in the auricle were markedly decreased under UVA irradiation, whereas those in sera were not affected. Furthermore, we examined the severity of sitafloxacin-induced phototoxicity under varied duration of UVA irradiation. The severity of phototoxicity increased with increasing duration of UVA irradiation, and statistical analysis showed a close correlation between the severity and the decreased area under the drug concentration curve under UVA irradiation ({Delta}AUCauricle). The severity was decreased with delay in commencement of UVA irradiation, indicating the importance of commencement time of irradiation in the experimental condition of the phototoxicity study. It might be attributed to the decrease in {Delta}AUCauricle after administration. These results suggest that sitafloxacin possesses milder phototoxic potential than lomefloxacin or sparfloxacin and is degraded in the auricular skin under UVA irradiation, and that the severity of phototoxicity is directly proportional to the {Delta}AUCauricle.

Key Words: phototoxicity; quinolone; sitafloxacin; ultraviolet-A; auricle; toxicokinetics; AUC.


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