Impact of body composition on pharmacokinetics of doxorubicin in children: a Glaser Pediatric Research Network study

Purpose We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer. Patients and methods Children between 1 and 21 years of age, receiving doxorubicin as an infusion of any duration <24 h on either a 1-day or 2-day schedule were eligible if they...

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Published inCancer chemotherapy and pharmacology Vol. 64; no. 2; pp. 243 - 251
Main Authors Thompson, Patrick A, Rosner, Gary L, Matthay, Katherine K, Moore, Theodore B, Bomgaars, Lisa R, Ellis, Kenneth J, Renbarger, Jamie, Berg, Stacey L
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.07.2009
Springer-Verlag
Springer
Springer Nature B.V
Subjects
Adolescent
Adult
Antineoplastic agents
Antineoplastic Agents - blood
Antineoplastic Agents - pharmacokinetics
Biological and medical sciences
Body Composition
Cancer Research
Child
Child, Preschool
Doxorubicin - analogs & derivatives
Doxorubicin - blood
Doxorubicin - pharmacokinetics
Female
Humans
Infant
Male
Medical sciences
Medicine
Medicine & Public Health
Metabolic Clearance Rate
Metabolic diseases
Neoplasm Staging
Neoplasms - blood
Neoplasms - diagnosis
Obesity
Obesity - blood
Oncology
Original Article
Pharmacology. Drug treatments
Pharmacology/Toxicology
Prognosis
Prospective Studies
Treatment Outcome
Young Adult
Pediatrics
Obesity
Pharmacokinetics
Doxorubicin
Doxorubicinol
Body composition
Human
Antineoplastic agent
DNA topoisomerase (ATP-hydrolysing)
Enzyme
Nutrition disorder
Enzyme inhibitor
Infant
Topoisomerase II inhibitor
Research
Isomerases
Network
Anthracyclins
Child
Nutritional status
Online AccessGet full text

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Abstract Purpose We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer. Patients and methods Children between 1 and 21 years of age, receiving doxorubicin as an infusion of any duration <24 h on either a 1-day or 2-day schedule were eligible if they had no significant abnormality of liver function tests, their dose of doxorubicin was not based on ideal body weight or otherwise “capped,” and they weighed >=12 kg. Body composition was measured by dual-energy X-ray absorptiometry. Doxorubicin and doxorubicinol concentration in plasma were measured by high pressure liquid chromatography. NONMEM was used to perform pharmacokinetic model fitting and S-PLUS was used to perform a post hoc analysis to examine the effect of body composition on pharmacokinetic parameters. Results Twenty-two subjects (16 male; 10 Hispanic, 10 Caucasian, 2 Asian) completed the study. The median age was 15.0 years (range 3.3-21.5), median weight was 51.5 kg (range 12.4-80), median BMI was 19.7 (range 13.2-30.0), and median body fat was 25% (range 15-36). The population mean clearance of doxorubicin was 420 ml/min/m². Doxorubicinol but not doxorubicin clearance was lower in patients with body fat greater than 30%. Conclusions Doxorubicinol clearance is decreased in children with >30% body fat. This finding is potentially important clinically, because doxorubicinol may contribute significantly to cardiac toxicity after doxorubicin administration. Further study of the body composition on doxorubicin and doxorubicinol pharmacokinetics and on clinical outcomes is warranted.
AbstractList Purpose We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer. Patients and methods Children between 1 and 21 years of age, receiving doxorubicin as an infusion of any duration <24 h on either a 1-day or 2-day schedule were eligible if they had no significant abnormality of liver function tests, their dose of doxorubicin was not based on ideal body weight or otherwise "capped," and they weighed >=12 kg. Body composition was measured by dual-energy X-ray absorptiometry. Doxorubicin and doxorubicinol concentration in plasma were measured by high pressure liquid chromatography. NONMEM was used to perform pharmacokinetic model fitting and S-PLUS was used to perform a post hoc analysis to examine the effect of body composition on pharmacokinetic parameters. Results Twenty-two subjects (16 male; 10 Hispanic, 10 Caucasian, 2 Asian) completed the study. The median age was 15.0 years (range 3.3-21.5), median weight was 51.5 kg (range 12.4-80), median BMI was 19.7 (range 13.2-30.0), and median body fat was 25% (range 15-36). The population mean clearance of doxorubicin was 420 ml/min/m². Doxorubicinol but not doxorubicin clearance was lower in patients with body fat greater than 30%. Conclusions Doxorubicinol clearance is decreased in children with >30% body fat. This finding is potentially important clinically, because doxorubicinol may contribute significantly to cardiac toxicity after doxorubicin administration. Further study of the body composition on doxorubicin and doxorubicinol pharmacokinetics and on clinical outcomes is warranted.
We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer. Children between 1 and 21 years of age, receiving doxorubicin as an infusion of any duration <24 h on either a 1-day or 2-day schedule were eligible if they had no significant abnormality of liver function tests, their dose of doxorubicin was not based on ideal body weight or otherwise "capped," and they weighed ≥12 kg. Body composition was measured by dual-energy X-ray absorptiometry. Doxorubicin and doxorubicinol concentration in plasma were measured by high pressure liquid chromatography. NONMEM was used to perform pharmacokinetic model fitting and S-PLUS was used to perform a post hoc analysis to examine the effect of body composition on pharmacokinetic parameters. Twenty-two subjects (16 male; 10 Hispanic, 10 Caucasian, 2 Asian) completed the study. The median age was 15.0 years (range 3.3-21.5), median weight was 51.5 kg (range 12.4-80), median BMI was 19.7 (range 13.2-30.0), and median body fat was 25% (range 15-36). The population mean clearance of doxorubicin was 420 ml/min/m2. Doxorubicinol but not doxorubicin clearance was lower in patients with body fat greater than 30%. Doxorubicinol clearance is decreased in children with >30% body fat. This finding is potentially important clinically, because doxorubicinol may contribute significantly to cardiac toxicity after doxorubicin administration. Further study of the body composition on doxorubicin and doxorubicinol pharmacokinetics and on clinical outcomes is warranted.
We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer.PURPOSEWe studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer.Children between 1 and 21 years of age, receiving doxorubicin as an infusion of any duration <24 h on either a 1-day or 2-day schedule were eligible if they had no significant abnormality of liver function tests, their dose of doxorubicin was not based on ideal body weight or otherwise "capped," and they weighed > or =12 kg. Body composition was measured by dual-energy X-ray absorptiometry. Doxorubicin and doxorubicinol concentration in plasma were measured by high pressure liquid chromatography. NONMEM was used to perform pharmacokinetic model fitting and S-PLUS was used to perform a post hoc analysis to examine the effect of body composition on pharmacokinetic parameters.PATIENTS AND METHODSChildren between 1 and 21 years of age, receiving doxorubicin as an infusion of any duration <24 h on either a 1-day or 2-day schedule were eligible if they had no significant abnormality of liver function tests, their dose of doxorubicin was not based on ideal body weight or otherwise "capped," and they weighed > or =12 kg. Body composition was measured by dual-energy X-ray absorptiometry. Doxorubicin and doxorubicinol concentration in plasma were measured by high pressure liquid chromatography. NONMEM was used to perform pharmacokinetic model fitting and S-PLUS was used to perform a post hoc analysis to examine the effect of body composition on pharmacokinetic parameters.Twenty-two subjects (16 male; 10 Hispanic, 10 Caucasian, 2 Asian) completed the study. The median age was 15.0 years (range 3.3-21.5), median weight was 51.5 kg (range 12.4-80), median BMI was 19.7 (range 13.2-30.0), and median body fat was 25% (range 15-36). The population mean clearance of doxorubicin was 420 ml/min/m(2). Doxorubicinol but not doxorubicin clearance was lower in patients with body fat greater than 30%.RESULTSTwenty-two subjects (16 male; 10 Hispanic, 10 Caucasian, 2 Asian) completed the study. The median age was 15.0 years (range 3.3-21.5), median weight was 51.5 kg (range 12.4-80), median BMI was 19.7 (range 13.2-30.0), and median body fat was 25% (range 15-36). The population mean clearance of doxorubicin was 420 ml/min/m(2). Doxorubicinol but not doxorubicin clearance was lower in patients with body fat greater than 30%.Doxorubicinol clearance is decreased in children with >30% body fat. This finding is potentially important clinically, because doxorubicinol may contribute significantly to cardiac toxicity after doxorubicin administration. Further study of the body composition on doxorubicin and doxorubicinol pharmacokinetics and on clinical outcomes is warranted.CONCLUSIONSDoxorubicinol clearance is decreased in children with >30% body fat. This finding is potentially important clinically, because doxorubicinol may contribute significantly to cardiac toxicity after doxorubicin administration. Further study of the body composition on doxorubicin and doxorubicinol pharmacokinetics and on clinical outcomes is warranted.
Purpose We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer. Patients and methods Children between 1 and 21 years of age, receiving doxorubicin as an infusion of any duration <24 h on either a 1-day or 2-day schedule were eligible if they had no significant abnormality of liver function tests, their dose of doxorubicin was not based on ideal body weight or otherwise “capped,” and they weighed ≥12 kg. Body composition was measured by dual-energy X-ray absorptiometry. Doxorubicin and doxorubicinol concentration in plasma were measured by high pressure liquid chromatography. NONMEM was used to perform pharmacokinetic model fitting and S-PLUS was used to perform a post hoc analysis to examine the effect of body composition on pharmacokinetic parameters. Results Twenty-two subjects (16 male; 10 Hispanic, 10 Caucasian, 2 Asian) completed the study. The median age was 15.0 years (range 3.3–21.5), median weight was 51.5 kg (range 12.4–80), median BMI was 19.7 (range 13.2–30.0), and median body fat was 25% (range 15–36). The population mean clearance of doxorubicin was 420 ml/min/m 2 . Doxorubicinol but not doxorubicin clearance was lower in patients with body fat greater than 30%. Conclusions Doxorubicinol clearance is decreased in children with >30% body fat. This finding is potentially important clinically, because doxorubicinol may contribute significantly to cardiac toxicity after doxorubicin administration. Further study of the body composition on doxorubicin and doxorubicinol pharmacokinetics and on clinical outcomes is warranted.
We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer. Children between 1 and 21 years of age, receiving doxorubicin as an infusion of any duration <24 h on either a 1-day or 2-day schedule were eligible if they had no significant abnormality of liver function tests, their dose of doxorubicin was not based on ideal body weight or otherwise "capped," and they weighed > or =12 kg. Body composition was measured by dual-energy X-ray absorptiometry. Doxorubicin and doxorubicinol concentration in plasma were measured by high pressure liquid chromatography. NONMEM was used to perform pharmacokinetic model fitting and S-PLUS was used to perform a post hoc analysis to examine the effect of body composition on pharmacokinetic parameters. Twenty-two subjects (16 male; 10 Hispanic, 10 Caucasian, 2 Asian) completed the study. The median age was 15.0 years (range 3.3-21.5), median weight was 51.5 kg (range 12.4-80), median BMI was 19.7 (range 13.2-30.0), and median body fat was 25% (range 15-36). The population mean clearance of doxorubicin was 420 ml/min/m(2). Doxorubicinol but not doxorubicin clearance was lower in patients with body fat greater than 30%. Doxorubicinol clearance is decreased in children with >30% body fat. This finding is potentially important clinically, because doxorubicinol may contribute significantly to cardiac toxicity after doxorubicin administration. Further study of the body composition on doxorubicin and doxorubicinol pharmacokinetics and on clinical outcomes is warranted.
Author Ellis, Kenneth J
Renbarger, Jamie
Moore, Theodore B
Berg, Stacey L
Matthay, Katherine K
Rosner, Gary L
Thompson, Patrick A
Bomgaars, Lisa R
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  fullname: Matthay, Katherine K
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  fullname: Moore, Theodore B
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  fullname: Bomgaars, Lisa R
– sequence: 6
  fullname: Ellis, Kenneth J
– sequence: 7
  fullname: Renbarger, Jamie
– sequence: 8
  fullname: Berg, Stacey L
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ISSN 0344-5704
1432-0843
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IsPeerReviewed true
IsScholarly true
Issue 2
Keywords Pediatrics
Obesity
Pharmacokinetics
Doxorubicin
Doxorubicinol
Body composition
Human
Antineoplastic agent
DNA topoisomerase (ATP-hydrolysing)
Enzyme
Nutrition disorder
Enzyme inhibitor
Infant
Topoisomerase II inhibitor
Research
Isomerases
Network
Anthracyclins
Child
Nutritional status
Language English
License http://www.springer.com/tdm
CC BY 4.0
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MergedId FETCHMERGED-LOGICAL-c454t-1119a1e410143f0d0efe6cc89bebdef143ccd7fd0bfa8fced4ae25ad5ae2dfc53
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ObjectType-Article-1
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content type line 14
content type line 23
PMID 19020877
PQID 213505140
PQPubID 48447
PageCount 9
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proquest_miscellaneous_46297459
proquest_journals_213505140
pubmed_primary_19020877
pascalfrancis_primary_21550114
crossref_citationtrail_10_1007_s00280_008_0854_z
crossref_primary_10_1007_s00280_008_0854_z
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PublicationDateYYYYMMDD 2009-07-01
PublicationDate_xml – month: 07
  year: 2009
  text: 2009-07-01
  day: 01
PublicationDecade 2000
PublicationPlace Berlin/Heidelberg
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PublicationTitle Cancer chemotherapy and pharmacology
PublicationTitleAbbrev Cancer Chemother Pharmacol
PublicationTitleAlternate Cancer Chemother Pharmacol
PublicationYear 2009
Publisher Berlin/Heidelberg : Springer-Verlag
Springer-Verlag
Springer
Springer Nature B.V
Publisher_xml – name: Berlin/Heidelberg : Springer-Verlag
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Snippet Purpose We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer. Patients and methods Children between 1...
Purpose We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer. Patients and methods Children between 1...
We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer. Children between 1 and 21 years of age,...
We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer. Children between 1 and 21 years of age,...
We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer.PURPOSEWe studied the relationship between...
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SubjectTerms Adolescent
Adult
Antineoplastic agents
Antineoplastic Agents - blood
Antineoplastic Agents - pharmacokinetics
Biological and medical sciences
Body Composition
Cancer Research
Child
Child, Preschool
Doxorubicin - analogs & derivatives
Doxorubicin - blood
Doxorubicin - pharmacokinetics
Female
Humans
Infant
Male
Medical sciences
Medicine
Medicine & Public Health
Metabolic Clearance Rate
Metabolic diseases
Neoplasm Staging
Neoplasms - blood
Neoplasms - diagnosis
Obesity
Obesity - blood
Oncology
Original Article
Pharmacology. Drug treatments
Pharmacology/Toxicology
Prognosis
Prospective Studies
Treatment Outcome
Young Adult
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Title Impact of body composition on pharmacokinetics of doxorubicin in children: a Glaser Pediatric Research Network study
URI https://link.springer.com/article/10.1007/s00280-008-0854-z
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