Personalizing intravenous (IV)
busulfan doses in children using therapeutic
drug monitoring (TDM) is an integral component of hematopoietic cell transplant. The authors sought to characterize initial dosing and TDM of IV
busulfan, along with factors associated with
busulfan clearance, in 729 children who underwent
busulfan TDM from December 2005 to December 2008. The initial IV
busulfan dose in children weighing ≤12 kg ranged 4.8-fold, with only 19% prescribed the package insert dose of 1.1 mg/kg. In those children weighing >12 kg, the initial dose ranged 5.4-fold, and 79% were prescribed the package insert dose. The initial
busulfan dose achieved the target exposure in only 24.3% of children. A wide range of
busulfan exposures were targeted for children with the same disease (eg, 39 target
busulfan exposures for the 264 children diagnosed with
acute myeloid leukemia). Considerable heterogeneity exists regarding when TDM is conducted and the number of pharmacokinetic samples obtained.
Busulfan clearance varied by age and dosing frequency but not by underlying disease. The authors- group is currently evaluating how using population pharmacokinetics to optimize initial
busulfan dose and TDM (eg, limited sampling schedule in conjunction with maximum a posteriori Bayesian estimation) may affect clinical outcomes in children.