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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 11/2015

01-11-2015 | Original Research Article

Age-Dependent Pharmacokinetics of Doxorubicin in Children with Cancer

Authors: Swantje Völler, Joachim Boos, Miriam Krischke, Gudrun Würthwein, Nina E. Kontny, Alan V. Boddy, Georg Hempel

Published in: Clinical Pharmacokinetics | Issue 11/2015

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Abstract

Background and Objective

Knowledge on the pharmacokinetics of doxorubicin, especially in children, is very limited with conflicting evidence concerning a possible age dependency in the pharmacokinetics. The aim of the current investigation was to assess, by using population pharmacokinetics, whether an age dependency in the clearance (CL) of doxorubicin exists.

Methods

Pharmacokinetic data of doxorubicin and its main metabolite doxorubicinol from 94 children (aged 0–18 years) from the EPOC-MS-001-Doxo trial were available. A population pharmacokinetic model was developed in NONMEM® 7.2.0.

Results

A linear three-compartment model for doxorubicin, with one additional compartment for doxorubicinol, gave the best fit to the data. All model parameters were linearly scaled on body surface area. Including a power function of age as a covariate for CL led to a further improvement of the model. Variation in genes encoding for enzymes involved in the metabolism or active transport of doxorubicin had no influence on the pharmacokinetics. Estimates of CL were lower (26.6 L/h/m2 in children aged >3 years and 21.1 L/h/m2 in children aged ≤3 years, p = 0.0004) in children aged <3 years, compared with older children.

Conclusions

This is the first model to describe the pharmacokinetics of doxorubicin in children, with a specific focus on infants and children aged <3 years. The lower CL in younger children should be considered together with the pharmacodynamics, especially the cardiotoxicity, when selecting the dose for future protocols.
Appendix
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Metadata
Title
Age-Dependent Pharmacokinetics of Doxorubicin in Children with Cancer
Authors
Swantje Völler
Joachim Boos
Miriam Krischke
Gudrun Würthwein
Nina E. Kontny
Alan V. Boddy
Georg Hempel
Publication date
01-11-2015
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 11/2015
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-015-0272-4

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