Reduction of doxorubicin (adriamycin) bone marrow toxicity

Doxorubicin (adriamycin), an antineoplastic antibiotic, is a potent suppressant of bone marrow. Previous studies on doxorubicin disposition indicated that its diversion from bone marrow in the first few minutes after administration should result in a marked decrease in total exposure to the drug (concentration X time) with a concomitant reduction in concentration-time-dependent toxicity. To test this hypothesis, the descending aorta of rabbits was occluded just proximal to the iliac bifurcation for 30 min to deprive bone marrow of blood flow. Both these rabbits and the control rabbits were given 5 mg/kg of doxorubicin intravenously, and the total white cell could in peripheral blood was monitored periodically for 15 days. The decrease in toxicity produced by the occlusion was quite evident by comparison of white cell counts and deaths in all groups. A possible mechanism of this effect was shown to be a decreased doxorubicin exposure of bone marrow tissue in the occluded animals as judged by relative doxorubicin concentration-time curves in rabbits with and without the aortic occlusion.