t-3762 and Body-Weight

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.

Topics: Alanine Transaminase; Animals; Anti-Infective Agents; Aspartate Aminotransferases; Body Weight; Cartilage, Articular; Dose-Response Relationship, Drug; Female; Fluoroquinolones; Injections, Intravenous; Male; Rats; Rats, Sprague-Dawley; Time Factors; Vocalization, Animal

A thirteen-week intravenous repeated dose toxicity study of T-3762, parenteral quinolone antimicrobial agent, and four-week recovery test was carried out in male and female cynomolgus monkeys at dosages of 26, 52 and 104 mg/kg. The following results were obtained. 1) There was no death of animals during administration period at any dose levels. In general signs, there was no abnormality at any dose levels. 2) In appetite, body weights and ophthalmological examination, there was no abnormality attributable to the treatment. 3) In urinalysis, hematological examination and biochemical examination, there was no abnormality attributable to the treatment. 4) In organ weights, macroscopic findings and histopathological findings, there was no abnormality attributable to the treatment. 5) From these results in this study, no-toxic dose level of T-3762 for cynomolgus monkeys is considered over 104 mg/kg.

Topics: Animals; Anti-Infective Agents; Body Weight; Eating; Female; Fluoroquinolones; Injections, Intravenous; Macaca fascicularis; Male; No-Observed-Adverse-Effect Level; Organ Size; Time Factors

A teratogenicity study of T-3762, an injectable new quinolone antibacterial agent, was conducted in Sprague-Dawley rats to determine the effects on dams and next generations. T-3762 was administered intravenously to pregnant rats at the dose levels of 26, 78 and 156 mg/kg/day from day 7 to day 17 of gestation, during the organogenesis. 1. In the dams, there were no effects on general condition, food intake, water intake and body weight in the T-3762 treated groups. There were no abnormal findings on the autopsy at the end of gestation and lactation periods in the T-3762 treated groups. 2. In the fetuses, there were no effects on the number of dead and live fetuses, sex ratio and body weight in the T-3762 treated groups. No external, visceral and skeletal abnormalities attributed to T-3762 were observed. 3. In the offspring, there were no effects on birth rate, viability, differentiation of external development, body weight, sensory function, emotionality, learning ability and reproductive performance in the T-3762 treated groups. From these results, no-toxic dose levels of T-3762 are considered to be 156 mg/kg for the general toxicity and the reproductive toxicity of parents and for the development of next generation, respectively.

Topics: Animals; Anti-Infective Agents; Body Weight; Embryonic and Fetal Development; Female; Fertility; Fluoroquinolones; Gestational Age; Growth; Male; No-Observed-Adverse-Effect Level; Organ Size; Pregnancy; Pregnancy, Animal; Rats; Rats, Sprague-Dawley