King M E, Naporn A, Young B, Howell S B
Cancer Treat Rep. 1984 Feb;68(2):361-6.
The effect of dipyridamole, an inhibitor of membrane nucleoside transport, on the uptake and toxicity of cytarabine was examined in normal and malignant tissues. Preliminary pharmacokinetic data were obtained in mice and humans to determine appropriate dipyridamole dosage ranges for in vitro testing. At concentrations achievable in man, dipyridamole produced 75% and 94% reductions in cytarabine uptake in freshly harvested normal mouse and human bone marrow cells, respectively. Under the same conditions, greater than 90% reductions in cytarabine uptake were also seen in both L1210 murine leukemia and HL-60 human leukemia cells. In addition, treatment with dipyridamole also reduced the growth inhibitory effects of cytarabine on HL-60 cells in culture and protected mice from toxic doses of this antimetabolite. These results demonstrate the ability of dipyridamole to modulate the activity of cytarabine in both murine and human cells.
在正常组织和恶性组织中研究了膜核苷转运抑制剂双嘧达莫对阿糖胞苷摄取和毒性的影响。在小鼠和人类中获得了初步药代动力学数据，以确定体外试验中双嘧达莫的合适剂量范围。在人体可达到的浓度下，双嘧达莫使新鲜收获的正常小鼠和人类骨髓细胞中阿糖胞苷的摄取分别降低了75%和94%。在相同条件下，L1210小鼠白血病细胞和HL-60人类白血病细胞中阿糖胞苷的摄取也降低了90%以上。此外，双嘧达莫治疗还降低了阿糖胞苷对培养的HL-60细胞的生长抑制作用，并保护小鼠免受这种抗代谢物的毒性剂量影响。这些结果证明了双嘧达莫在小鼠和人类细胞中调节阿糖胞苷活性的能力。
