Pharmacokinetics of aclarubicin and its metabolites in humans and their disposition in blood cells.

The pharmacokinetics of aclarubicin, a new anthracycline antibiotic, was studied in five patients with acute leukemia or in L1210 cell suspension. Aclarubicin disappeared very rapidly from plasma and whole blood after administration at a dose of 20 mg per patient by iv bolus injection. The concentration of active metabolite M1, on the other hand, increased for up to 2 or 4 hrs after administration and exceeded that of aclarubicin, and then remained at much higher concentrations than aclarubicin for up to 24 hrs after administration. In addition, the levels of aclarubicin and its metabolites in whole blood were much higher than the corresponding plasma levels in four of the patients. The drug concentrations in blood cells of 11 patients determined 4 hrs after administration showed a significant positive correlation with leukocyte counts. Moreover, the concentration of aclarubicin and its metabolites was found to be much higher in the leukocyte fraction than in the erythrocyte fraction in vivo and in vitro. These findings indicate that aclarubicin and its metabolites in blood cells were mainly accumulated in leukocytes. In the study of intracellular drug distribution in L1210 cells, the largest amount of aclarubicin was incorporated into the nuclear fraction. This suggests a close relationship between the pronounced drug accumulation in leukocytes and the high affinity of aclarubicin for DNA.