Patient selection
This retrospective study included 87 busulfan measurements in 54
consecutive children (age, 0.2–19.2 years) who received intravenous
busulfan at the National Center for Child Health and Development from
August 2015 to May 2020. The study was approved by the ethics committee
of the National Center for Child Health and Development (approval
number: 1964), and written informed consent was obtained from the
guardian of each patient.
Busulfan dosing and pharmacokinetic analysis
Thirteen patients received body weight-based busulfan dosing (0.8–1.2
mg/kg)7 without test dose. Forty-one patients received
a test dose lower than the body weight-based busulfan dose, and the
first dose was determined based on target AUC determined by the
pharmacokinetics parameters obtained with the test dose. All patients
were administered intravenous busulfan as a 2-h infusion every 6 h for
four days, and pharmacokinetic analysis was performed based on the first
dose. Blood samples at 3–5 time points per patient were collected at 1,
2, 3, 4, and 6 h from the start of busulfan infusion and processed using
the dried blood spot method. Plasma busulfan concentrations were
measured by liquid chromatography with tandem mass
spectrometry.8 Actual AUC0–∞ values
were calculated from the data on plasma concentrations at all time
points by applying the one-compartment model using the Phoenix®
WinNonlin 7.0 pharmacokinetic analysis software (Certara LP, Princeton,
NJ, USA).