Peak plasma concentrations of doxorubicin in children with acute lymphoblastic leukemia or non-Hodgkin lymphoma

Purpose: The peak plasma concentrations seem to play an important role in the toxicity of the anthracyclines. As there are only limited data in the literature about the distribution of doxorubicin in children, we assessed the peak plasma concentrations of doxorubicin in pediatric patients. Patients and methods: We collected 87 plasma samples at the end of infusion from 27 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) treated with 30 mg/m(2) doxorubicin as a 1- or 2-h infusion once weekly for four weeks in the ALL-BFM 95 or NHL-BFM 95 protocol. Plasma concentrations of doxorubicin were quantified by capillary electrophoresis, and the peak plasma levels for a uniform 2-h infusion were calculated. Results: The geometric mean of all samples was 273 mug/l with a geometric coefficient of variation of 46.0%. This is in accordance with the peak plasma concentrations expected from simulations based on literature data from adults. High inter-individual as well as substantial intra-individual variability was observed. Girls had slightly higher peak plasma levels than boys. Age, weight, and body mass index as well as laboratory parameters had no influence on the peak plasma concentrations. No cumulation of doxorubicin during therapy was observed. Conclusion: The peak plasma concentrations are similar in adults and children for both the absolute values as well as the variability, this indicates that there are no major differences in the distribution of doxorubicin in children and adults.