Temafloxacinの関節毒性試験

To determine the arthrotoxicity of temafloxacin hydrochloride (TMFX) in immature animals, TMFX was orally administered to 4-week-old rats (12 rats of each group and sex) at doses of 30, 100 and 300mg/kg and 3-month-old dogs (3 dogs of each group and sex) at doses of 10, 30 and 90mg/kg for 7 days.<BR>1) No remarkable clinical or pathological changes were seen in immature rats throughout the treatment or recovery period.<BR>2) In observing the gait of immature dogs, abnormal flexion of the carpal joints was seen in 3 male and 2 female dogs in the 90mg/kg group, and 1 male in the 30mg/kg dose group during the treatment period. This abnormality was observed throughtout the treatment period after its appearance. In the recovery period, this abnormality persisted 2-3 days after withdrawal in 1 male dog in each 30mg/kg and 90mg/kg group, but it disappeared later on.<BR>3) Blister-like lesions or erosions in the articular cartilage were grossly obseeved in all dogs with abnormal gait and 1 female dog with normal gait in the 90mg/kg group.<BR>4) Corresponding to the gross lesions, rarefaction of cartilage matrix and fissuring were histopathologically seen at the end of the treatment period. Chondrocytic regeneration and fibrocartilage-like metaplasia regarded as a process to repair articular cartilage damage were observed in the area surrounding fissures at the end of the recovery period. Edema of subsynovial connective tissue with stratification of synovial lining cells was only observed in dogs in the 90mg/kg group at the end of the treament period.<BR>From the above results, the arthrotoxicity dose of TMFX was considered to be over 300mg/kg in immature rats and 30mg/kg in immature dogs.