Vol.58 No.S-2 October 2010
Toxicity studies of tosufloxacin tosilate hydrate in juvenile animals and class effects studies
1)Research Laboratories, Toyama Chemical Co., Ltd., 2-4-1 Shimookui, Toyama, Japan
2)Shin Nippon Biomedical Laboratories, Ltd.
Abstract
To examine the toxicity of tosufloxacin tosilate hydrate(TFLX) in juvenile animals, a single oral dose study in rats and repeated oral dose studies in rats and dogs were conducted. Effects of TFLX on articular cartilage, QT interval, and blood glucose, known class effects of quinolone antibiotics, were examined.
In the single oral dose toxicity study in 7-day-old rats, the lethal dose was >6,000 mg/kg. In the 1 month repeated oral dose study in 7-day-old rats, 1 male died and transient body weight gain suppression was observed in survival at 3,000 mg/kg. Crystals were observed in the lumen of renal tubules at 1,000 mg/kg and higher and also observed in mature rats. The above changes were not observed at 300 mg/kg. In the 1 month repeated oral dose study in 3-week-old dogs, decrease in food consumption and body weight gain suppression were observed at 300 mg/kg and higher but also in norfloxacin(NFLX) and ciprofloxacin hydrochloride hydrate(CPFX) groups. No abnormality was observed at 150 mg/kg.
Articular toxicity was examined in juvenile (3-month-old) dogs administered TFLX orally for 2 weeks. Small blisters or erosion were observed on the shoulder articular cartilage at >50 mg/kg but was milder than NFLX or CPFX.
In QT interval studies, slight hERG current suppression (5%, using hERG-expressing HEK293 cells) was observed at >10 μmol/L, but no effect was seen on blood pressure, heart rate, or electrocardiogram in dogs up to 100 mg/kg.
In study on blood glucose and insulin levels in dogs, no effect was observed after a single oral administration of TFLX up to 600 mg/kg.
In conclusion, the effect of TFLX on articular cartilage was milder than NFLX and CPFX, no other specific toxicity or enhanced toxicity was seen in juvenile animals. No obvious effects were observed on QT interval or blood glucose or insulin levels.
Key word
tosufloxacin, juvenile animal, adverse effect
Received
April 20, 2010
Accepted
June 9, 2010
Jpn. J. Chemother. 58 (S-2): 12-23, 2010
