Two-point limited sampling strategy is necessary to estimate the area
under the concentration-time curve for intravenous busulfan in infants
and young children
Abstract
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.