[Three months intravenous repeated dose toxicity study of T-3762 in rats]

A three months intravenous repeated dose toxicity study of T-3762, a novel parenteral quinolone antibacterial agent, was carried out in rats at dose levels of 4, 13, 39, 130 mg/kg. Fifteen rats of each sex were used in each group. Out of these, 5 rats of each sex were used for the recovery study. The following results were obtained. 1. There were no death caused by T-3762 within the study period. In clinical signs, the squeaks during injection in 130 mg/kg group were observed, but they decreased day by day. In body weight changes, a tendency to very slight decrease of weight gain in male 130 mg/kg group were seen, but there was no significant difference from control group. In food and water consumption, there was no abnormality. 2. There were no abnormality caused by T-3762 in urinalysis, hematological examination and ophthalmological examination. 3. In blood chemistry examinations, increase of A/G ratio was seen in 13, 39 and 130 mg/kg groups, but it showed tendency of recovery after withdrawal period. 4. In macroscopic and histological findings, erosion and cavitation of the articular cartilage were seen in 3 of 20 rats in 130 mg/kg group and 1 of 20 rats in 39 mg/kg group. 5. Non-toxic dose levels is estimated to 13 mg/kg, that showed no abnormality in the articular cartilage in this study.