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

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Abstract
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.