Modulation of cytarabine uptake and toxicity by dipyridamole

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.