An exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity
| Autor: | Vickie E. Baracos, Vijaya L. Damaraju, Linda J. McCargar, Tony Reiman, Michelle Kuzma, Carla M. Prado, Michael B. Sawyer, John R. Mackey, Isac S. F. Lima, Robert R. Bies |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Cancer Research medicine.medical_specialty Neutrophils medicine.medical_treatment Population Breast Neoplasms Pharmacology Toxicology Gastroenterology Body Mass Index Liver Function Tests Pharmacokinetics Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Distribution (pharmacology) Pharmacology (medical) Prospective Studies education Aged Epirubicin education.field_of_study Chemotherapy Antibiotics Antineoplastic Chemistry Area under the curve Organ Size Middle Aged Liver Oncology Chemotherapy Adjuvant Area Under Curve Toxicity Body Composition Lean body mass Female Tomography X-Ray Computed medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 67:93-101 |
| ISSN: | 1432-0843 0344-5704 |
| DOI: | 10.1007/s00280-010-1288-y |
| Popis: | 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. 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). 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. 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. |
| Databáze: | OpenAIRE |
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