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Effect of weight and maturation on busulfan clearance in infants and small children undergoing hematopoietic cell transplantation

  • Author(s): Savic, RM
  • Cowan, MJ
  • Dvorak, CC
  • Pai, SY
  • Pereira, L
  • Bartelink, IH
  • Boelens, JJ
  • Bredius, RGM
  • Wynn, RF
  • Cuvelier, GDE
  • Shaw, PJ
  • Slatter, MA
  • Long-Boyle, J
  • et al.

Published Web Location

http://10.0.3.248/j.bbmt.2013.08.014
No data is associated with this publication.
Abstract

Little information is currently available regarding the pharmacokinetics (PK) of busulfan in infants and small children to help guide decisions for safe and efficacious drug therapy. The objective of this study was to develop an algorithm for individualized dosing of i.v. busulfan in infants and children weighing ≤12 kg, that would achieve targeted exposure with the first dose of busulfan. Population PK modeling was conducted using intensive time-concentration data collected through the routine therapeutic drug monitoring of busulfan in 149 patients from 8 centers. Busulfan PK was well described by a 1-compartment base model with linear elimination. The important clinical covariates affecting busulfan PK were actual body weight and age. Based on our model, the predicted clearance of busulfan increases approximately 1.7-fold between 6 weeks to 2 years of life. For infants age <5 months, the model-predicted doses (mg/kg) required to achieve a therapeutic concentration at steady state of 600-900 ng/mL (area under the curve range, 900-1350 μM·min) were much lower compared with standard busulfan doses of 1.1 mg/kg. These results could help guide clinicians and inform better dosing decisions for busulfan in young infants and small children undergoing hematopoietic cell transplantation. © 2013 American Society for Blood and Marrow Transplantation.

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