Background: Therapeutic drug monitoring for busulfan is important to prevent adverse events and improve outcomes in stem cell transplantation. We investigated intravenous busulfan pharmacokinetics and evaluated the utility of limited sampling strategy (LSS) as a simple method to estimate the area under the concentration-time curve (AUC). Procedure: The study comprised 87 busulfan measurements in 54 children who received intravenous busulfan between August 2015 and May 2020. AUCs were calculated from 3–5 blood sampling points in each patient, and the correlation between AUC and plasma concentrations (ng/mL) at 1, 2, 3, 4, and 6 h after initiating busulfan infusion (C1, C2, C3, C4, and C6, respectively). Results: By one-point sampling strategy, the most accurate predicted AUC was based on C6 (r2 = 0.789; precision, 11.0%) in all patients. The predicted AUC based on C6 was highly precise (r2 = 0.937; precision, 5.9%) in adolescent patients weighing > 23 kg, but the correlation was poor in infants and young children weighing ≤23 kg (r2 = 0.782; precision, 11.4%). By two-point sampling strategy, the predicted AUC based on C3 and C6 showed the most favorable performance (r2 = 0.943; precision, 6.4%), even in infants and young children, whereas the predicted AUC based on C3 and C6 was acceptable (r2 = 0.963; precision, 5.7%). Conclusions: The AUC of busulfan can be predicted based on C6 in adolescent patients. However, there was substantial inter-individual variation in busulfan pharmacokinetics in infants and young children, in whom two-point LSS was necessary for accurate AUC prediction.
