Accurate Prediction of Initial Busulfan Exposure Using a Test Dose With 2- and 6-Hour Blood Sampling in Adult Patients Receiving a Twice-Daily Intravenous Busulfan-Based Conditioning Regimen.

This study aimed to predict the area under the curve (AUC) of the initial busulfan dose using a test dose with the sparse sampling scheme in adult patients who underwent hematopoietic cell transplant. A test dose of 0.8 mg/kg busulfan was used 2 days before twice-daily intravenous busulfan-based conditioning regimens were administered. The AUC and the clearance (CL) were calculated for both the test dose and the first dose (AUCT , CLT , AUC1, and CL1 ) by noncompartmental analysis. The sparse sampling schemes of the test dose were developed by Bayesian method based on the population pharmacokinetic model. The optimal sparse sampling schemes were determined by evaluating the mean prediction error, the root mean square error, the absolute mean prediction error, and Bland-Altman plot. The mean AUC1 was 7.20 ± 1.48 mg • h/L, which ranged from 4.70 to 9.46 mg • h/L. The AUC1 was below the therapeutic concentration of 7.38 mg • h/L in 45% (9 of 20) of the patients. The CLT of 3.05 ± 0.56 mL/min/kg was not significantly different with the CL1 of 3.03 ± 0.69 mL/min/kg (P = .901). A sampling scheme at 2 and 6 hours after the test dose was developed to predict the AUCT (mean prediction error of 1.64%, root mean square error of 6.17%, and absolute mean prediction error of 4.94%). Additionally, the Bland-Altman plot showed that the 2-sampling scheme provided an acceptably accurate prediction of the AUC1 . A test dose with a 2-sampling scheme was sufficient to personalize the initial busulfan dosing in hematopoietic cell transplant recipients.