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. 2025 Feb 11;95(1):32.
doi: 10.1007/s00280-025-04757-w.

New approach to busulfan dosing in infants and children based on a population pharmacokinetic analysis

Frank M Balis  1   2 , Elizabeth Rieger  3 , Nancy J Bunin  3 , JoAnn Gardiner  4 , Leslie M Shaw  4 , Timothy S Olson  3 , Michael C Milone  4
Affiliations

New approach to busulfan dosing in infants and children based on a population pharmacokinetic analysis

Frank M Balis et al. Cancer Chemother Pharmacol. .

Abstract

Purpose: Apply population pharmacokinetic modeling to a single institution busulfan therapeutic drug monitoring (TDM) data set from infants and children to refine dosing methods.

Methods: One-compartment pharmacokinetic model was fit to busulfan TDM data from 328 infants and children with malignant and non-malignant diseases treated with busulfan-containing transplant conditioning regimens. Age-dependence of busulfan clearance scaled to body weight and body surface area (BSA) was compared, and busulfan AUC was simulated for a BSA-scaled dose of 100 mg/m2 combined with a BSA-banded dosing table for infants and children with a BSA < 0.5 m2.

Results: Busulfan clearance scaled to body weight is age-dependent. Clearance in children ≤ 3 years (0.234 L/[h•kg]) is higher than the typical value for the population, (0.205 L/[h•kg]), and 48% of children < 5 years have subtherapeutic busulfan AUCs after the first dose. Busulfan clearance scaled to BSA (typical value, 5.47 L/[h•m2]) is more uniform across the pediatric age span, except for infants (≤ 1 year, 4.27 L/[h•m2]). Simulated busulfan AUCs with a dose of 100 mg/m2 for patients with a BSA ≥ 0.5 m2 combined with a BSA-banded dosing table for patients with a BSA < 0.5 m2 achieved a therapeutic AUC after the first dose in 49% more patients than body weight scaled doses.

Conclusion: Our model predicts a greater proportion of children would achieve a therapeutic busulfan AUC after the first dose with a dose of 100 mg/m2/d combined with the infant dosing table for patients with a BSA < 0.5 m2 compared to body weight-scaled dosing.

Keywords: Body surface area; Body weight; Busulfan; Dosing table; Stem cell transplantation; Therapeutic drug monitoring.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Busulfan AUCinf as a function of patient age after the first dose in 328 patients. AUCinf for patients on the q6h schedule was multiplied by 4 to give the AUCinf achieved with 4 doses administered over 24 h (equivalent to the AUCinf from the daily dosing schedule)
Fig. 2
Fig. 2
Busulfan clearance (CLi) scaled to body weight (A) and body surface area (B) according to patient age and by dosing schedule for the first dose of busulfan in 328 patients. The C.V. for CLi normalized to BSA (L/[h•m2]) was 23%, normalized to body weight (L/[h•kg]) was 28%, and not normalized to body size (L/h) was 62%
Fig. 3
Fig. 3
Simulated busulfan AUCinf for (A) 328 patients using a busulfan dose of 100 mg/m2 and for (B) the 258 patients with a BSA ≥ 0.5 m2 using a dose of 100 mg/m2 plus from the BSA-banded dosing table for the 70 patients with a BSA < 0.5 m2. The green horizontal lines are the upper and lower bound of the therapeutic range
See this image and copyright information in PMC

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