Population pharmacokinetics of doxorubicin: establishment of a NONMEM model for adults and children older than 3 years

Purpose The aim of the current investigation was to develop a population pharmacokinetic model for doxorubicin and doxorubicinol that could provide improved estimated values for the pharmacokinetic parameters clearance of doxorubicin, volume of distribution of the central compartment, clearance of d...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 2013-03, Vol.71 (3), p.749-763
Main Authors: Kontny, Nina E., Würthwein, Gudrun, Joachim, Boos, Boddy, Alan V., Krischke, Miriam, Fuhr, Uwe, Thompson, Patrick A., Jörger, Markus, Schellens, Jan H. M., Hempel, Georg
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Aging - metabolism
Analysis of Variance
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - pharmacokinetics
Antineoplastic agents
Biological and medical sciences
Biotransformation
Body Mass Index
Cancer Research
Child
Child, Preschool
Databases, Factual
Dose-Response Relationship, Drug
Doxorubicin - administration & dosage
Doxorubicin - pharmacokinetics
Humans
Infusions, Intravenous
Medical sciences
Medicine
Medicine & Public Health
Middle Aged
Models, Statistical
Oncology
Original Article
Pharmacology. Drug treatments
Pharmacology/Toxicology
Population
Reproducibility of Results
Young Adult
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Summary:Purpose The aim of the current investigation was to develop a population pharmacokinetic model for doxorubicin and doxorubicinol that could provide improved estimated values for the pharmacokinetic parameters clearance of doxorubicin, volume of distribution of the central compartment, clearance of doxorubicinol and volume of distribution of the metabolite compartment for adults and children older than 3 years. A further aim was to investigate the potential influence of the covariates body surface area, body weight, body height, age, body mass index, sex and lean body mass on the pharmacokinetic parameters. Methods Three different datasets, two containing data from adults and one containing data from adults and children, were merged and the combined dataset was analysed retrospectively. In total, the combined dataset contained 934 doxorubicin and 935 doxorubicinol plasma concentrations from 82 patients [64 adults and 18 children (
ISSN:0344-5704
1432-0843
DOI:10.1007/s00280-013-2069-1