Pharmacokinetics of Mitoxantrone in Plasma and Leukemic Cells During Treatment of Patients with Acute Non-Lymphocytic Leukemia

Abstract

The pharmacokinetics of mitoxantrone was studied in the plasma and peripheral leukemic cells in 14 patients receiving induction treatment for acute non-lymphocytic leukemia. The disappearance of mitoxantrone from plasma was biphasic with a mean distribution half life of 10.4 minutes and a mean elimination half life of 17.1 hours. At the end of the infusion, the mean mitoxantrone concentration in leukemic cells was 9.6 times (range 2.1-22.7) higher than in plasma and remained relatively stable in the cells until the next infusion following 24 hours after the first. The area under the concentration-time curve (AUC_0-20h) in leukemic cells was 23-191 times larger than the AUC_0-α in plasma. In the individual patient there was no correlation between the AUC in leukemic cells and AUC in plasma. Since mitoxantrone acts intracellularly, concentrations in the leukemic cells might predict the antileukemic effect better than plasma concentrations.

Key Words:

• Mitoxantrone
• pharmacokinetics
• leukemic cells
• acute non-lymphocytic
• leukemia