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).