[Toxicity studies on T-3262 in rat upon intravenous injection for 14 days].
T-3262 is a new antibacterial drug which has been developed for oral administration in clinical use. It is known that T-3262 has cytotoxicity in cultured mammalian cells. Therefore, it is necessary to determine the cytotoxicity-related effects of T-3262 (if it is absorbed in a large quantity in animal). In this study, the toxicity of T-3262 was investigated in Sprague-Dawley rats upon intravenous injection of T-3262 at 50 mg/kg/day for 14 days, and the results were compared to those obtained with ofloxacin (OFLX) and mitomycin C (MMC). The results are summarized as follows. 1. In the T-3262-treated group, no animal died and no abnormal changes occurred regarding general symptoms during the treatment. There were no significant abnormalities in hematological, blood biochemical, ophthalmological and anatomical examinations nor changes in nucleate cells of bone marrow and myelogram. Crystal sediment (test material-like) was observed in urine of 8 of 10 rats examined. The weights of heart and prostate (including seminal vesicle) decreased and the weight of cecum increased. In histological examinations, dilatation of renal tubuli was observed in kidneys of 2 of 7 rats examined. 2. In the OFLX-treated group, no treatment-related changes were found. In histological examinations, the dilatation of renal tubuli was not observed. 3. In the MMC-treated group, the following changes were observed: decrease in body weight gain, in white blood cell (WBC) counts and number of nucleate cell in bone marrow, increase in myeloid vs. erythroid ratio. Hypoplasia of bone marrow was also observed. From the above results, no significant abnormalities occurred in rats treated intravenously with 50 mg/kg/day of T-3262 for 14 days. The cytotoxicity of T-3262 observed in cultured mammalian cells was not reflected in animals in this study.
Yoneda
T
T
Research Laboratory, Toyama Chemical Co., Ltd.
Nakamura
S
S
Nojima
Y
Y
Nagai
A
A
Nagasawa
M
M
Nishio
Y
Y
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D024841:Fluoroquinolones; D006403:Hematologic Tests; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects; D008297:Male; D016685:Mitomycin; D008937:Mitomycins / Q000633:toxicity; D009287:Naphthyridines; D015242:Ofloxacin / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D008937:Mitomycins; D009287:Naphthyridines; D016685:Mitomycin; D015242:Ofloxacin; C055185:tosufloxacin