An exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity

Carla M M Prado, Isac S F Lima, Vickie E. Baracos, Robert Bies, Linda J. McCargar, Tony Reiman, John R. MacKey, Michelle Kuzma, Vijaya L. Damaraju, Michael B. Sawyer

Research output: Contribution to journalArticle

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Abstract

Purpose: Although body composition has emerged as an important predictor of drug efficacy and toxicity, explanations for this association are unclear. Our goal was to investigate relationships between lean body mass (LBM), liver size/function and epirubicin pharmacokinetics (PK) and toxicity. Methods: Data from a clinical study (n = 24) of patients with breast cancer receiving adjuvant intravenous FE100C chemotherapy were used to examine relationships between LBM, liver size, and epirubicin clearance. Muscle tissue and liver mass were measured by analysis of computerized tomography cross-sectional images, and an extrapolation of muscle mass to total LBM compartment was employed. Population PK analysis of epirubicin was undertaken to test effects of body composition on epirubicin clearance and area under the curve (AUC). Results: Estimated LBM was extremely variable in this cohort ranging from 32.9 to 67.3 kg. LBM was associated with neutrophil nadir (r = 0.5, P = 0.023), and mean LBM was lower for patients presenting with toxicity compared to those where toxicity was absent (41.6 vs. 56.2 kg, P = 0.002); 33% of variance in clearance was explained by LBM and aspartate aminotransferase (AST). Liver mass was not related to epirubicin clearance likely due to larger livers presenting with larger fat content, but liver attenuation (degree of fat infiltration) and AST were associated with AUC. Conclusion: To our knowledge, this is the first study to examine relationships between LBM, liver mass/function and epirubicin PK and toxicity. This exploratory work investigates the notion of organs and tissues having distinctive contributions to the distribution and metabolism of antineoplastic drugs.

Original languageEnglish
Pages (from-to)93-101
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume67
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Epirubicin
Pharmacokinetics
Body Composition
Liver
Toxicity
Chemical analysis
Aspartate Aminotransferases
Area Under Curve
Muscle
Fats
Tissue
Muscles
Chemotherapy
Computerized tomography
Drug-Related Side Effects and Adverse Reactions
Infiltration
Extrapolation
Metabolism
Antineoplastic Agents
Neutrophils

Keywords

  • Body composition
  • Clearance
  • Epirubicin
  • Lean body mass
  • Liver attenuation
  • Liver mass
  • Pharmacokinetics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

An exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity. / Prado, Carla M M; Lima, Isac S F; Baracos, Vickie E.; Bies, Robert; McCargar, Linda J.; Reiman, Tony; MacKey, John R.; Kuzma, Michelle; Damaraju, Vijaya L.; Sawyer, Michael B.

In: Cancer Chemotherapy and Pharmacology, Vol. 67, No. 1, 01.2011, p. 93-101.

Research output: Contribution to journalArticle

Prado, CMM, Lima, ISF, Baracos, VE, Bies, R, McCargar, LJ, Reiman, T, MacKey, JR, Kuzma, M, Damaraju, VL & Sawyer, MB 2011, 'An exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity', Cancer Chemotherapy and Pharmacology, vol. 67, no. 1, pp. 93-101. https://doi.org/10.1007/s00280-010-1288-y
Prado, Carla M M ; Lima, Isac S F ; Baracos, Vickie E. ; Bies, Robert ; McCargar, Linda J. ; Reiman, Tony ; MacKey, John R. ; Kuzma, Michelle ; Damaraju, Vijaya L. ; Sawyer, Michael B. / An exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity. In: Cancer Chemotherapy and Pharmacology. 2011 ; Vol. 67, No. 1. pp. 93-101.
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AU - Reiman, Tony

AU - MacKey, John R.

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