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 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.

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Acknowledgments

This work was funded in part by the Thrasher Foundation.

Author informationAuthors and Affiliations

Texas Children’s Cancer Center, 6621 Fannin St., MC3-3320, Houston, TX, 77030, USA

Patrick A. Thompson, Lisa R. Bomgaars & Stacey L. Berg

University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 1411, Houston, TX, 77030, USA

Gary L. Rosner

UCSF School of Medicine, 505 Parnassus Ave., Rm. M647, San Francisco, CA, 94143, USA

Katherine K. Matthay

UCLA David Geffen School of Medicine, 10833 Le Conte Ave., Rm. A2-312, Los Angeles, CA, 90095, USA

Theodore B. Moore

Children’s Nutrition Research Center, 1100 Bates St., Rm. 4020, Houston, TX, 77030, USA

Kenneth J. Ellis

Indiana University School of Medicine, 702 Barnhill Dr., Rm. 4340, Indianapolis, IN, 46202, USA

Jamie Renbarger

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Thompson, P.A., Rosner, G.L., Matthay, K.K. et al. Impact of body composition on pharmacokinetics of doxorubicin in children: a Glaser Pediatric Research Network study. Cancer Chemother Pharmacol 64, 243–251 (2009). https://doi.org/10.1007/s00280-008-0854-z

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Received: 19 February 2008

Accepted: 07 October 2008

Published: 20 November 2008

Issue Date: July 2009

DOI: https://doi.org/10.1007/s00280-008-0854-z