Busulfan in infants to adult hematopoietic cell transplant recipients: A population pharmacokinetic model for initial and Bayesian dose personalization.

Publication Type:

Journal Article

Source:

Clinical cancer research : an official journal of the American Association for Cancer Research (2013)

Keywords:

2013, Clinical Research Division, December 2013

Abstract:

Personalizing intravenous (IV) busulfan doses to a target plasma concentration at steady state (Css) is an essential component of hematopoietic cell transplantation (HCT). We sought to develop a population pharmacokinetic model to predict IV busulfan doses over a wide age spectrum (0.1 - 66 years) that accounts for differences in age and body size. Experimental design: A population pharmacokinetic model based on normal fat mass and maturation based on post-menstrual age was built from 12,380 busulfan concentration-time points obtained after IV busulfan administration in 1,610 HCT recipients. Subsequently, simulation results of the initial dose necessary to achieve a target Css with this model were compared with pediatric-only models.