Tvete S T, Elsayed E A, Hope A, Clausen G
Eur J Cancer Clin Oncol. 1983 Jan;19(1):127-34. doi: 10.1016/0277-5379(83)90407-8.
The uptake of adriamycin (Adm) by normal tissues and by sarcomas transplanted to both kidneys in rats was studied at 10 min following constant rate infusion of Adm 5 mg/kg body wt into one renal artery, during 3 and 10 min. Since the selectively infused kidney extracted only about 20% of the total dose, the present model provides a direct comparison of systemic versus selective i.a. infusions in each individual. Tumor Adm uptake was about 6 times higher on the selectively infused side. Adm uptake by tumor and normal renal tissue was proportional to the concentration X time product of Adm in arterial blood, in spite of highly different blood peak concentrations at different infusion rates. Ten-minute systemic intravenous infusion of the Adm dose, with concurrent infusion of ricin, 3 micrograms/kg, into one renal artery tended to increase Adm uptake by the tumors on both sides. This indicates a systemic rather than a local effect of ricin: ricin reduced Adm uptake by red blood cells and normal solid tissues and thus resulted in a delayed Adm clearance from the total plasma volume. In contrast, the relationship between tumor uptake and the concentration X time product of Adm in plasma was not affected by ricin, explaining the increased tumor uptake.
在以5mg/kg体重的阿霉素（Adm）持续输注到大鼠一侧肾动脉10分钟、3分钟和10分钟后，研究了正常组织以及移植到双侧肾脏的肉瘤对阿霉素的摄取情况。由于选择性输注的肾脏仅摄取了总剂量的约20%，因此本模型可对每个个体的全身输注与选择性动脉内输注进行直接比较。在选择性输注的一侧，肿瘤对阿霉素的摄取约高6倍。尽管在不同输注速率下血药峰浓度差异很大，但肿瘤和正常肾组织对阿霉素的摄取与动脉血中阿霉素的浓度×时间乘积成正比。将阿霉素剂量进行10分钟的全身静脉输注，同时向一侧肾动脉输注3μg/kg的蓖麻毒素，往往会增加双侧肿瘤对阿霉素的摄取。这表明蓖麻毒素具有全身而非局部作用：蓖麻毒素降低了红细胞和正常实体组织对阿霉素的摄取，从而导致阿霉素从总血浆量中的清除延迟。相反，血浆中阿霉素的浓度×时间乘积与肿瘤摄取之间的关系不受蓖麻毒素的影响，这解释了肿瘤摄取增加的原因。
