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Age influence on the kinetic disposition and metabolism of epirubicin in breast cancer patients

Grant number: 14/06846-1
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2014
Effective date (End): January 31, 2016
Field of knowledge:Biological Sciences - Pharmacology - Clinical Pharmacology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Vera Lúcia Lanchote
Grantee:Leandro Francisco Pippa
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The present study aims to assess the effect of age on doxorubicin kinetic disposition and metabolism in breast cancer patients. Forty (40) breast cancer patients in the first cycle of treatment with the doxorubicin-cyclophosphamide regimen will be divided into two groups: control group including younger patients (< 60 years) and study group including elderly patients (> 60 years). Patients will receive doxorubicin infusion (75 mg/m²) for approximately 2 h. Serial blood and urine samples will be collected for 48 hours following the infusion start. LC-MS/MS technique will be applied to analyse total and free concentrations of doxorubicin and doxorubicinol in plasma, as well as the total concentrations in urine. Patients will be genotyped for CBR1 and CBR2 enzymes through polymorphisms identification by allelic discrimination applying real-time polymerase chain reaction technique. Population pharmacokinetics model will be developed using NONMEM software (Non-Linear Mixed Effect Level) in collaboration with researchers at University College London (London, England). The results will be expressed as means, 95% confidence intervals, medians and 25-75% percentiles. Mann-Whitney test (significance set at p < 0.05) will be used to evaluate the influence of age on doxorubicin and its metabolite doxorubicinol pharmacokinetics. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PIPPA, LEANDRO FRANCISCO; DE OLIVEIRA, MILENA LOCCI; ROCHA, ADRIANA; DE ANDRADE, JURANDYR MOREIRA; LANCHOTE, VERA LUCIA. Total, renal and hepatic clearances of doxorubicin and formation clearance of doxorubicinol in patients with breast cancer: Estimation of doxorubicin hepatic extraction ratio. Journal of Pharmaceutical and Biomedical Analysis, v. 185, JUN 5 2020. Web of Science Citations: 0.

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