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

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/10(9) cells (bolus injections) and 10310 +/- 5510 ng/10(9) 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/10(9) cells and 2850 +/- 1720 ng/10(9) 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.