Ito K, Handa J, Irie Y, Ezura H, Kumagai M, Irie Y, Suzuki A, Miyamoto K, Yamashita T, Tsubosaki M, Matsuda A, Konoha N
Jpn J Antibiot. 1978 Dec;31(12):767-802.
Subacute toxicity and its recovery of pepleomycin sulfate was studied in both sexes of beagle dogs. At dose levels of 2.4, 1.2 and 0.6 mg/kg, pepleomycin was administered intramuscularly to dogs for 30 successive days. Two dogs of the 1.2 mg/kg dose group were used for recovery test for 35 days. As general symptoms, the decrease of food intake, the loss of body weight, ulceration of foot pad, nail root necrosis and onychoptosic, ulcer of tongue and labia, and alopecia, dermatitis and necrosis at friction sites were observed the more severely in high dose groups, as those in bleomycin were. The death occurred in the 2.4 mg/kg dose group of both sexes. The lesions of liver and kidney were recognized in the 2.4 and 1.2 mg/kg dose groups of both sexes on biochemical, histopathological or urinary findings. Additionally slight fibrous change of lung was observed in all dose groups. Generally subacute toxicity of pepleomycin was revealed approximately in the same as or in a little stronger degree than that of bleomycin, and its recovery was hardly recognized during its period. The maximum safety dose in this studies is estimated to be between 0.3 and 0.6 mg/kg in dogs.
对硫酸培普利欧霉素在比格犬雌雄两性中的亚急性毒性及其恢复情况进行了研究。以2.4、1.2和0.6mg/kg的剂量水平,对犬连续30天进行肌肉注射培普利欧霉素。1.2mg/kg剂量组的两只犬用于35天的恢复试验。作为一般症状,高剂量组中观察到的食物摄入量减少、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的脱发、皮炎和坏死比博来霉素组更为严重。2.4mg/kg剂量组的雌雄两性均出现死亡。在生化、组织病理学或尿液检查结果中,2.4和1.2mg/kg剂量组的雌雄两性均发现肝脏和肾脏病变。此外,在所有剂量组中均观察到肺部有轻微的纤维性改变。总体而言,培普利欧霉素的亚急性毒性与博来霉素大致相同或略强,在此期间几乎未观察到其恢复情况。本研究中犬的最大安全剂量估计在0.3至0.6mg/kg之间。