Differences in the plasma kinetics of daunorubicin in normal and leukemic rats

The plasma pharmacokinetics of the anthracycline drug daunorubicin in doses of 1 and 10 mg/kg body weight were compared in normal and leukemic inbred Sutton-August rats (50-70 x 10(9) leukemic cells/1 blood). The area under the plasma concentration versus time curve was about 25 times larger in the leukemic rats at both dose levels. The data indicate that daunorubicin has a lower volume of distribution in leukemic rats as compared with normals. The large reduction in plasma clearance of daunorubicin in the leukemic rats can to some extent be explained by impairment of hepatic and renal functions but the results indicate that the leukemic state per se was of importance for the observed pharmacokinetic differences. This finding may be of importance for the treatment of patients with a high leukemic cell load, since higher retention of the drug in the central compartment leads to lower concentrations in poorly vascularized tissues, which favours the development of resistant leukemic cell clones.