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.