Development of a population pharmacokinetic model using the NONMEN software (Non-linear mixed effect model) for oral busulfan dosage individualization in patients undergoing hematopoietic stem cell transplantation.

• Grant number: 12/03150-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2012
• End date: February 28, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Clinical Pharmacology
• Principal Investigator: Vera Lúcia Lanchote
• Grantee: Francine Attié de Castro
• Supervisor: Oscar e Della Pasqua
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Universiteit Leiden, Netherlands
• Associated to the scholarship: 09/17545-4 - Enantioselectivity on the kinetic disposition and metabolism of cyclophosphamide and dose ajustment of busulfan in patients undergoing stem cell transplantation, BP.DR

Abstract

Busulfan (BU) is an alkylating agent commonly administered in a pre-conditioning hematopoietic stem cell transplantation (HSCT). BU is a drug with narrow therapeutic index and high interindividual variability in pharmacokinetics. Therapeutic monitoring of oral BU is necessary for success of bone marrow transplantation and it is already well described in literature. Conventional therapeutic monitoring of busulfan requires analysis of 15 blood samples. Thus, the aim of this project is to develop a population pharmacokinetic model for oral BU in order to reduce the number of blood samples analysis (from fifteen to approximately two) in patients undergoing HSTC. To develop the population pharmacokinetic model of oral busulfan will be used the data of my PhD regular project (FAPESP process: 2009 / 17545-4). The population pharmacokinetic model will be developed using the NONMEN software in collaboration with University of Leiden. The development of the model will allow to reduce the number of blood samples necessary to do the therapeutic monitoring of oral BU in patients undergoing allogeneic bone marrow, will facilitate the treatment, reduce the mortality rate related to BU toxicity and favor the clinical outcome of patients undergoing HSCT.