COMPARISON OF THE INTRACELLULAR PHARMACOKINETICS OF DAUNORUBICIN AND IDARUBICIN IN PATIENTS WITH ACUTE-LEUKEMIA

Five patients with acute non-lymphoblastic leukemia were treated with a mixture of daunorubicin 50 mg/m(2) and idarubicin 10 mg/m(2) given a s a short-time infusion. Daunorubicin, idarubicin and the main metabol ites daunorubicinol and idarubicinol were separated and the concentrat ions in plasma and leukemic cells were determined by HPLC. Although id arubicin was given in one-fifth of the dose, the intracellular peak co ncentration was 70% of that of daunorubicin. The initial elimination o f idarubicin from leukemic cells was somewhat faster but in the termin al phase the drug was retained longer than daunorubicin. Intracellular concentrations of both metabolites were low and probably of little im portance for the activity of the drug. We conclude that the intracellu lar pharmacokinetics of idarubicin, with higher peak concentration and longer terminal retention, is a possible explanation for the higher t oxicity and suggested better antileukemic effect of this drug.