Phototoxic retinal degeneration and toxicokinetics of sitafloxacin, a quinolone antibacterial agent, in mice

• Published in: Archives of toxicology Vol. 75; no. 7; pp. 395 - 399
• Main Authors: SHIMODA, Kohji, OKAWARA, Satoshi, KATO, Michiyuki
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.09.2001; Springer Nature B.V
• Subjects: Animals; Anti-Infective Agents - pharmacokinetics; Anti-Infective Agents - toxicity; Biological and medical sciences; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Female; Fluoroquinolones; Injections, Intravenous; Medical research; Medical sciences; Mice; Mice, Inbred BALB C; Pharmacology. Drug treatments; Photoreceptor Cells, Vertebrate - drug effects; Photoreceptor Cells, Vertebrate - radiation effects; Retina; Retinal Degeneration - chemically induced; Retinal Degeneration - metabolism; sitafloxacin; Time Factors; Toxicity: eye; Ultraviolet Rays; UVA radiation; Intravenous administration; Toxicity; Rodentia; Retina; Eye disease; Vertebrata; Fluoroquinolone derivatives; Mammalia; Mouse; Animal; Phototoxicity; Degeneration; Antibacterial agent; Pharmacokinetics; Quinolone derivatives; Sitafloxacin
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s002040100263

We examined drug concentrations and the incidence of retinal degeneration in the eyes of albino BALB/c mice after a single intravenous administration of sitafloxacin plus a 4 h period of UVA irradiation. Retinal degeneration was induced at 40 mg/kg or more plus UVA irradiation, and there was little decrease in ocular sitafloxacin concentration under UVA irradiation. We then examined the incidence of retinal degeneration with various periods of UVA irradiation in BALB/c mice given a single intravenous administration of 40 mg/kg sitafloxacin. Retinal degeneration occurred in all the groups receiving UVA irradiation immediately after sitafloxacin administration, whereas no retinal degeneration occurred in the groups receiving UVA irradiation starting 30 min or later after administration. In addition, we examined both the retinal degeneration and auricular inflammation in BALB/c mice given a 7-day repeated administration of sitafloxacin at 1, 3.3 and 10 mg/kg per day, which never induce retinal or auricular change by a single administration. Retinal degeneration was not induced at any dose level, although auricular skin inflammation was augmented by repeated administration. These results suggest that the occurrence of retinal degeneration depends on maximum ocular sitafloxacin concentration during UVA irradiation, whereas the severity of auricular inflammation is directly proportional to the total decrease in area under the drug concentration curve for auricular sitafloxacin under UVA irradiation. This difference between retinal degeneration and auricular inflammation may derive from their respective mechanisms of pathogenesis.