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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 R ; McCargar, Linda J ; Reiman, Tony ; Mackey, John R ; Kuzma, Michelle ; Damaraju, Vijaya L ; Sawyer, Michael B

Cancer chemotherapy and pharmacology, 2011-01, Vol.67 (1), p.93-101 [Periódico revisado por pares]

Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag

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Título:
exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity
Autor: Prado, Carla M. M ; Lima, Isac S. F ; Baracos, Vickie E ; Bies, Robert R ; McCargar, Linda J ; Reiman, Tony ; Mackey, John R ; Kuzma, Michelle ; Damaraju, Vijaya L ; Sawyer, Michael B
Assuntos: Adult ; Aged ; Antibiotics, Antineoplastic - administration & dosage ; Antibiotics, Antineoplastic - adverse effects ; Antibiotics, Antineoplastic - pharmacokinetics ; Antineoplastic agents ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Area Under Curve ; Biological and medical sciences ; Body Composition ; Body Mass Index ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Cancer Research ; Chemotherapy, Adjuvant - methods ; Clearance ; epirubicin ; Epirubicin - administration & dosage ; Epirubicin - adverse effects ; Epirubicin - pharmacokinetics ; Female ; Humans ; lean body mass ; Liver - metabolism ; Liver attenuation ; Liver Function Tests ; Liver mass ; Medical sciences ; Medicine ; Medicine & Public Health ; Middle Aged ; Neutrophils - metabolism ; Oncology ; Organ Size ; Original Article ; pharmacokinetics ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Prospective Studies ; Tomography, X-Ray Computed
É parte de: Cancer chemotherapy and pharmacology, 2011-01, Vol.67 (1), p.93-101
Notas: http://dx.doi.org/10.1007/s00280-010-1288-y
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Descrição: 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.
Editor: Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag
Idioma: Inglês

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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 R ; McCargar, Linda J ; Reiman, Tony ; Mackey, John R ; Kuzma, Michelle ; Damaraju, Vijaya L ; Sawyer, Michael B

Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag

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