Development of a population pharmacokinetic model for Busulfan in hematopoietic stem cell transplantation

Abstract

The applications of Busulfan as a chemotherapeutic agent has been disappearing over the years as better therapeutic alternatives have been released. Nowadays it is mainly used for some myeloproliferative diseases and the conditioning process previous to Hematopoietic Stem Cell Transplantation. During this project, data was collected from 98 patients taking Busulfan for the aforementioned conditioning, which were further used to develop a population pharmacokinetic model aiming to predict plasma concentrations of the drug in patients. A one-compartment model best described the data, which adjusted its interindividual variability for clearance (CL/F) with a Typical Value of 11.0 L/h, and for the distribution volume (V/F) with a Typical Value of 42.7 L. Both parameters showed a better fit to the data by the application of the Adjusted Ideal Body Weight covariate to explain the residual error. The final model went through two internal validation processes and will be used henceforth in the clinical pharmacokinetic unit of the Catalan Oncology Institute targeting those patients with potential to achieve toxic concentrations and avoid adverse events derived from its use.