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

• Grant number: 14/06846-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2014
• End date: January 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Clinical Pharmacology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Vera Lúcia Lanchote
• Grantee: Leandro Francisco Pippa
• Host 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)

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. (14/06846-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PIPPA, Leandro Francisco. Pharmacokinetics, metabolism and urinary excretion of doxorubicin in breast cancer patients. 2016. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.