Gralla E J, Fleischman R W, Luthra Y K, Stadnicki S W
Toxicology. 1979 Aug;13(3):263-73.
The toxic effects of Adriamycin were studied following i.v. administration of from 10.0 mg/kg to 0.039 mg/kg (200--0.780 mg/m2) to beagle dogs, and from 5.83 mg/kg to 0.625 mg/kg (49.9--7.5 mg/m2) in rhesus monkeys by a variety of short and long term treatment schedules. 5 daily doses and 1 dose every 3 weeks were given for both species and, only in dogs, as single injections, 10 daily treatments and 5 daily doses followed by 9 days rest, repeated 3 times. In both species, short term administration of toxic doses caused weight losses, anorexia, diarrhea, atypical oesophageal and intestinal mucosa, bone marrow hypoplasia, lymphoid atrophy and alopecia. Specific adverse responses seen only in monkeys were hypocalcemia, hypomagnesemia, atypical buccal mucosa and reddish urinary pigmentation. Testicular degeneration and prostatic atrophy were produced in dogs. The triweekly treatment schedule caused an additional toxicity at lower doses. In both species a cardiotoxicity syndrome developed with pulmonary oedema and centrolobular hepatic necrosis, plus focal necrosis and vacuolization in cardiac myocytes. Clinical signs of cardiac dysfunction were EKG arrhythmias in dogs, and peripheral oedema, ascites and hydrothorax in monkeys.
通过多种短期和长期治疗方案，对成年比格犬静脉注射10.0 mg/kg至0.039 mg/kg（200 - 0.780 mg/m²），对恒河猴静脉注射5.83 mg/kg至0.625 mg/kg（49.9 - 7.5 mg/m²），研究阿霉素的毒性作用。两种动物均给予每日5次剂量和每3周1次剂量，仅对犬给予单次注射、每日10次治疗、每日5次剂量后休息9天并重复3次。在两种动物中，短期给予毒性剂量均导致体重减轻、厌食、腹泻、非典型食管和肠黏膜、骨髓发育不全、淋巴萎缩和脱发。仅在猴中出现的特异性不良反应为低钙血症、低镁血症、非典型颊黏膜和尿液色素沉着发红。犬出现睾丸退化和前列腺萎缩。每3周治疗方案在较低剂量时产生额外毒性。两种动物均出现心脏毒性综合征，伴有肺水肿和肝小叶中心坏死，以及心肌细胞局灶性坏死和空泡化。犬心脏功能障碍的临床体征为心电图心律失常，猴为外周水肿、腹水和胸腔积液。
