Tamoxifen population pharmacokinetics in breast cancer patients: metabolism study, genetic polymorphism, hormonal status and age

• Grant number: 14/16360-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): February 01, 2015
• Effective date (End): September 30, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Clinical Pharmacology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Vera Lúcia Lanchote
• Grantee: João Paulo Bianchi Ximenez
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 16/20613-5 - Tamoxifen population pharmacokinetics in breast cancer patients: metabolism, genetic polymorphism, hormonal status and age, BE.EP.DR

Abstract

The study hypothesis is to investigate the influence of age and hormonal status on tamoxifen kinetic and metabolism in breast cancer patients. Thus, two groups of patients will be defined according to age and hormonal status, a pre-menopausal group (age < 50 years) and another postmenopausal (age > 60 years). Blood samples will be collated from patients within 24 hours after tamoxifen daily dose to determine tamoxifen total and free plasma concentrations and total concentration of its metabolites endoxifen and 4-OH-tamoxifen by a LC-MS/MS; added to the determination CYP2D6, CYP3A and P-gp in vivo activity using, respectively, pharmacological markers metoprolol, midazolam and fexofenadine; also the genotypes of the CYP2D6 and CYP3A4/5, ABCC2 and ABCB1 gene by Taqman allelic discrimination. The population pharmacokinetic model will be developed using the software NONMEM (Non-linear mixed effect level). The results will express as means, 95% confidence intervals, medians and percentiles 25-75%. Mann-Whitney test (significance fixed at p <0.05) will be used to evaluate the influence of age and hormonal status on the pharmacokinetics of tamoxifen and its metabolites. (AU)

Academic Publications

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

XIMENEZ, João Paulo Bianchi. Non-compartmental and population pharmacokinetics of tamoxifen in patients undergoing treatment for breast cancer: metabolism, hormonal status and genetic polymorphism. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.