Vol.55 No.S-1 October 2007
Three-month repeated oral dose toxicity study of garenoxacin in rats
Research Laboratories, Toyama Chemical Co., Ltd., 2-4-1 Shimookui, Toyama, Japan
Abstract
Garenoxacin mesilate hydrate(GRNX) was administered to male (50, 100, 200 and 400 mg/kg) and female (100, 200, 400 and 800 mg/kg) SD rats orally for 3 months, and toxicity was assessed. Reversibility of toxic changes was also assessed in males receiving 200 and 400 mg/kg, and females receiving 400 and 800 mg/kg following 1-month withdrawal. In males, deposition of lipid droplets in hepatocytes was seen at doses of 100 mg/kg and above; suppression of body weight gain, an increase in alkaline phosphatase, and a decrease in heart weight were seen at doses of 200 mg/kg and above; and decreases in triglyceride and salivary glands weight were seen at dose of 400 mg/kg. In females, an increase in alkaline phosphatase, a decrease in salivary glands weight, and lesions in the articular cartilage were seen at doses of 400 mg/kg and above; and decreases in triglyceride and heart weight, and deposition of lipid droplets in hepatocytes were seen at dose of 800 mg/kg. At the end of recovery, osteochondrosis in the articular cartilage was seen in males receiving 400 mg/kg and females receiving 800 mg/kg. As other changes, changes (soft feces and dilatation in cecal lumen, etc.) attributed to change in intestinal bacterial flora due to the antibacterial activity of GRNX were seen in each group.
From the above, no observable adverse effect level was estimated at 50 mg/kg for males and 200 mg/kg for females. In toxicokinetics, a sex difference was seen in plasma concentration, and AUC0-∞ in females was about one-fourth to one-third of that in males.
All of these changes were also seen in repeated dose toxicity studies of fluoroquinolone antimicrobial agents, and no peculiar changes in GRNX were seen.
Key word
garenoxacin, des-fluoro(6)-quinolone, rat, subacute toxicity
Received
May 11, 2007
Accepted
August 22, 2007
Jpn. J. Chemother. 55 (S-1): 34-41, 2007
