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Purpose <p>Apply population pharmacokinetic modeling to a single institution busulfan therapeutic drug monitoring (TDM) data set from infants and children to refine dosing methods.</p> Methods <p>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/m<sup>2</sup> combined with a BSA-banded dosing table for infants and children with a BSA &lt; 0.5 m<sup>2</sup>.</p> Results <p>Busulfan clearance scaled to body weight is age-dependent. Clearance in children ≤ 3 years (0.234&#xa0;L/[h•kg]) is higher than the typical value for the population, (0.205&#xa0;L/[h•kg]), and 48% of children &lt; 5 years have subtherapeutic busulfan AUCs after the first dose. Busulfan clearance scaled to BSA (typical value, 5.47&#xa0;L/[h•m<sup>2</sup>]) is more uniform across the pediatric age span, except for infants (≤ 1 year, 4.27&#xa0;L/[h•m<sup>2</sup>]). Simulated busulfan AUCs with a dose of 100 mg/m<sup>2</sup> for patients with a BSA ≥ 0.5 m<sup>2</sup> combined with a BSA-banded dosing table for patients with a BSA &lt; 0.5 m<sup>2</sup> achieved a therapeutic AUC after the first dose in 49% more patients than body weight scaled doses.</p> Conclusion <p>Our model predicts a greater proportion of children would achieve a therapeutic busulfan <i>AUC</i> after the first dose with a dose of 100 mg/m<sup>2</sup>/d combined with the infant dosing table for patients with a BSA &lt; 0.5 m<sup>2</sup> compared to body weight-scaled dosing.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月11日

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  • Frank M. Balis,
  • Elizabeth Rieger,
  • Nancy J. Bunin,
  • JoAnn Gardiner,
  • Leslie M. Shaw,
  • Timothy S. Olson,
  • Michael C. Milone

摘要

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.