Cellular and plasma adriamycin concentrations in long-term infusion therapy of leukemia patients

Abstract

To determine whether long-term adriamycin (ADM) infusions resulted in cellular ADM concentrations at least comparable to those observed after bolus injections, ADM cellular and plasma concentrations were measured in 18 patients with leukemia. ADM was administered at 30 mg/m2 per day for 3 days, either as bolus injections or as 4-, 8-, or 72-h infusions. Negligible accumulation of plasma ADM was observed. Peak plasma ADM concentrations after bolus injections were 1640 +/- 470 ng/ml (n = 7). Maximum levels were 176 +/- 34 ng/ml during 4-h infusion (n = 5); 85 +/- 50 ng/ml during 8-h infusion (n = 4); and 47 +/- 5 ng/ml (n = 2) after 72-h infusion. ADM concentrations in nucleated blood and bone marrow cells correlated well (r = 0.82, n = 47). ADM accumulated in leukemic cells up to 30-100 times the plasma concentrations. The shorter the administration time-span, the higher the peak leukemic cell concentration and the greater the loss of drug immediately after the end of the administration. The final cellular ADM half-life was approximately 85-110 h. After long-term infusion and bolus injection of the same dose, similar areas under the curve for plasma or leukemic blast cell ADM concentrations were attained. Since comparable therapeutic efficacy was observed in all regimens, the antileukemic effect appeared not to be related to the peak plasma concentrations, while acute toxicity phenomena decreased with increasing duration of the infusion. Long-term ADM infusion deserves more attention in the treatment of patients with anthracyclines.