A 13-week oral toxicity study of prulifloxacin (NM441) in rats followed by a 5-week recovery test

Abstract

A repeated dose toxicity study of prulifloxacin, a new antibacterial agent, was conducted in Sprague-Dawley rats. Male and female rats were given the test material orally for 13 weeks at doses of 0 (control), 30, 170 and 1000 mg/kg. After discontinuation of the treatment, a 5-week recovery test was also conducted. Salivation, soft feces, reduced body weight gain and increased water consumption were seen in the 1000 mg/kg group. There were no treatment-related effects on survival and food consumption. Ophthalmoscopic and hematologic examinations failed to show any abnormalities attributable to the treatment. Urinalysis revealed increased urine volume and decreased K+ excretion in the 1000 mg/kg group. Blood chemical examination showed increased BUN, decreased triglyceride, K+, Cl- and total protein in the 1000 mg/kg group. Pathological changes caused by the treatment were as follows. Renal tubular nephrosis with crystalline substance was observed in the 170 and 1000 mg/kg groups. Renal weight was increased and crystalline substance was noted in the lumen of the urinary bladder in the 1000 mg/kg group. Cecal distention with increased its organ weight was observed in all dose groups and swelling of its absorptive cells was seen in the 170 and 1000 mg/kg groups. Swelling of jejunal goblet cells was observed in the 1000 mg/kg group. In femoral articular cartilage, focal accumulation of chondrocytes, small cavities and proliferation of fibrous tissue were seen in the 170 and 1000 mg/kg groups. The above-mentioned changes were reversible except for renal tubular nephrosis and cecal distention with its increased organ weight, of which the degree and frequency, however, were lowered. The cecal distention in the 30 mg/kg group was considered to be attributable to the pharmacological effect of the test material. The results show that the NOAEL of prulifloxacin is 30 mg/kg for 13-week repeated dose toxicity in rats.