Ito K, Handa J, Irie Y, Ezura H, Kumagai M, Irie Y, Suzuki A, Hagiwara T, Yamane H, Miyamoto K, Yamashita T, Tsubosaki M, Matsuda A, Konoha N
Jpn J Antibiot. 1979 Mar;32(3):387-450.
Chronic toxicity and its recovery of pepleomycin sulfate was studied in both sexes of beagle dogs. At dose levels of 0.3, 0.15 and 0.075 mg/kg, pepleomycin was administered intramuscularly to dogs for 180 successive days. Two dogs of the 0.15 mg/kg dose group were used for recovery test for 35 days. As general findings, the decrease of food intake, the loss of body weight, ulceration of foot pad, nail root necrosis and onychoptosis, ulcer of tongue and labia, and alopecia, dermatitis and necrosis at friction sites were observed more severely in the 0.3 mg/kg dose group of both sexes, especially in male, than those in bleomycin were. In the dose groups of 0.15 and 0.075 mg/kg, their findings were observed as slightly as those in bleomycin were. The death occurred in the 0.3 mg/kg dose group of both sexes. The lesions of liver and kidney were recognized in the 0.3 mg/kg dose group of both sexes, severely in male, on histopathological findings. Additionally severe fibrosis of lung was observed in one of the 0.3 mg/kg dose group of female. In general chronic toxicity of pepleomycin was revealed more severely in the 0.3 mg/kg dose group than that of bleomycin was, but in the dose groups of 0.15 and 0.075 mg/kg difference between their toxicities was not significant. In addition, chronic toxicity of pepleomycin in dogs showed more severely in male and its recovery was hardly recognized during its period. The maximum safety dose in this studies was estimated to be between 0.075 and 0.15 mg/kg in dogs.
对雄性和雌性比格犬进行了硫酸培普利霉素的慢性毒性及其恢复情况的研究。以0.3、0.15和0.075mg/kg的剂量水平，对犬连续180天进行肌肉注射培普利霉素。0.15mg/kg剂量组的两只犬用于35天的恢复试验。一般观察结果显示，0.3mg/kg剂量组的雄性和雌性犬，尤其是雄性犬，食欲减退、体重减轻、脚垫溃疡、指甲根部坏死和脱甲、舌和阴唇溃疡以及摩擦部位脱发、皮炎和坏死的情况比博来霉素组更严重。在0.15和0.075mg/kg剂量组中，观察到的结果与博来霉素组相似。0.3mg/kg剂量组的雄性和雌性犬均有死亡发生。组织病理学检查发现，0.3mg/kg剂量组的雄性和雌性犬均有肝肾损伤，雄性犬更为严重。此外，0.3mg/kg剂量组的一只雌性犬出现了严重的肺纤维化。总体而言，培普利霉素在0.3mg/kg剂量组的慢性毒性比博来霉素更严重，但在0.15和0.075mg/kg剂量组，其毒性差异不显著。此外，培普利霉素对犬的慢性毒性在雄性犬中表现更严重，且在此期间几乎未观察到恢复情况。本研究中犬的最大安全剂量估计在0.075至0.15mg/kg之间。
