Comparison of the intracellular pharmacokinetics of daunorubicin and idarubicin in patients with acute leukemia

Leuk Res. 1994 Apr;18(4):293-7. doi: 10.1016/0145-2126(94)90032-9.

Abstract

Five patients with acute non-lymphoblastic leukemia were treated with a mixture of daunorubicin 50 mg/m2 and idarubicin 10 mg/m2 given as a short-time infusion. Daunorubicin, idarubicin and the main metabolites daunorubicinol and idarubicinol were separated and the concentrations in plasma and leukemic cells were determined by HPLC. Although idarubicin was given in one-fifth of the dose, the intracellular peak concentration was 70% of that of daunorubicin. The initial elimination of idarubicin from leukemic cells was somewhat faster but in the terminal phase the drug was retained longer than daunorubicin. Intracellular concentrations of both metabolites were low and probably of little importance for the activity of the drug. We conclude that the intracellular pharmacokinetics of idarubicin, with higher peak concentration and longer terminal retention, is a possible explanation for the higher toxicity and suggested better antileukemic effect of this drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Daunorubicin / analogs & derivatives
  • Daunorubicin / pharmacokinetics*
  • Female
  • Humans
  • Idarubicin / pharmacokinetics*
  • Leukemia, Myeloid, Acute / metabolism*
  • Male
  • Middle Aged

Substances

  • idarubicinol
  • daunorubicinol
  • Idarubicin
  • Daunorubicin