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


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 microg/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.


CONCLUSIONS
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.
Hempel
Georg
G
Institut für Pharmazeutische Chemie, Westfälische Wilhems-Universität, Münster, Germany. hempege@uni-muenster.de
Flege
Silke
S
Würthwein
Gudrun
G
Boos
Joachim
J
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D004317:Doxorubicin / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D012737:Sex Factors
D004317:Doxorubicin