Key Points
- To evaluate and compare the pharmacokinetics of unconjugated and DNA-conjugated daunorubicin and doxorubicin in plasma and leukemic cells of patients with acute nonlymphoblastic leukemia.
- Evaluated drug and metabolite pharmacokinetics across 19 treatment courses in 16 patients with acute nonlymphoblastic leukemia.
- Measured plasma and intracellular concentrations following treatment with unconjugated or DNA-conjugated daunorubicin and doxorubicin.
- Daunorubicin reached higher peak intracellular levels, whereas doxorubicin demonstrated prolonged cellular retention and higher tissue affinity.
- DNA-conjugation increased mean intracellular doxorubicin accumulation by 60% but did not markedly alter daunorubicin uptake.
- The cell/plasma concentration ratio was higher for daunorubicin than for daunorubicinol, and no intracellular doxorubicinol was detected.
Structured PICO
PPopulation16 patients with acute nonlymphoblastic leukemia
IInterventionDaunorubicin and doxorubicin (unconjugated or DNA-conjugated) administered during 19 courses of treatment
OOutcomePharmacokinetics in plasma and leukemic cells (clearance, volume of distribution, intracellular peak concentrations, retention)surrogate
Differences in cellular pharmacokinetics between daunorubicin and doxorubicin, as well as enhanced intracellular accumulation of doxorubicin via DNA-conjugation, may explain their clinical activity spectra and potential for reduced cardiotoxicity.