Introduction
Therapeutic drug monitoring for busulfan is important for improving clinical outcomes in hematopoietic stem cell transplantation.1 Busulfan exposure, expressed as the area under the concentration-time curve (AUC), is an important parameter for monitoring therapeutic efficacy and adverse events. A high busulfan AUC increases the risk of adverse events such as sinusoidal obstruction syndrome/hepatic veno-occlusive disease,2 while a low busulfan AUC is associated with higher probability of graft failure or disease relapse.1 Therefore, busulfan dosage is adjusted to a target AUC of 75–100 mg/L × h in myeloablative conditioning regimens.3 Recent studies have demonstrated that reduced-intensity conditioning regimens with busulfan doses adjusted according to a target AUC of 45–65 mg/L × h are effective in chronic granulomatous disease and Wiskott-Aldrich syndrome.4,5 Busulfan pharmacokinetics varies greatly among individuals,6 and target AUC depends on the conditioning regimen and underlying disease; thus, it is clinically essential to calculate the busulfan AUC.
AUC is determined using the pharmacokinetic modeling software or the linear trapezoidal method; however, pharmacokinetic analyses require frequent blood sampling. Limited sampling strategies (LSSs) are used to estimate the AUC from a limited number of blood samples. Furthermore, LSSs permit the easy estimation of AUC without using the pharmacokinetic modeling software, and the drug dosage can be immediately adjusted according to the blood concentrations, such as the trough value, which is of great importance in clinical practice. In the present study, we investigated the pharmacokinetics of intravenous busulfan and evaluated the utility of LSS as an accurate and simple method to estimate AUC in pediatric patients undergoing hematopoietic transplantation.