Leukemic cell and plasma daunomycin concentrations after bolus injection and 72 h infusion

Summary

The effect of the duration of daunomycin (DNM) infusion on leukemic cell drug concentrations was evaluated. Cellular and plasma DNM concentrations were measured in 20 patients with acute non-lymphocytic leukemia. DNM 45 mg/m² was administered either as a bolus injection or as a 4-, 8- or 72-h constant-rate infusion during 3 consecutive days. Peak plasma DNM levels amounted to 227±116 ng/ml after bolus injection and were only 16±6 ng/ml after 72-h DNM infusions. Terminal plasma DNM half-lives were 14±4 h. Peak leukemic cell DNM concentrations at the 3rd day of administration were 16810±2580 ng/10⁹ cells (bolus injections) and 10310±5510 ng/10⁹ cells (72-h infusions). The areas under the cellular curve were similar and independent of the duration of the DNM infusion. Peak leukemic cell daunomycinol (DNMol) concentrations were respectively 3500 ± 1600 ng/10⁹ cells and 2850±1720 ng/10⁹ cells. Cellular DNM terminal half-life was 13±4 h. DNM concentrations in nucleated blood and bone marrow cells correlated well (r=0.93, n=26). Long-term infusion produced less severe side effects. Therapeutic efficacy was maintained during long-term infusion.