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Related Experiment Videos

Busulfan disposition in children.

L B Grochow1, W Krivit, C B Whitley

  • 1Division of Pharmacology and Experimental Therapeutics, Johns Hopkins Oncology Center, Baltimore, MD 21205.

Blood
|April 15, 1990
PubMed
Summary

Pediatric busulfan pharmacokinetics differ significantly from adults, with lower concentrations and higher clearance rates. This suggests a need for tailored dosing strategies in children undergoing bone marrow transplantation.

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Area of Science:

  • Pharmacology
  • Pediatric Oncology
  • Pharmacokinetics

Background:

  • Busulfan is used in pediatric myeloablative therapy for bone marrow transplantation.
  • Children exhibit low severe toxicity and engraftment failure rates with oral busulfan.
  • Understanding pediatric busulfan disposition is crucial for optimizing treatment.

Purpose of the Study:

  • To evaluate the pharmacokinetic disposition of oral busulfan in pediatric patients.
  • To compare busulfan pharmacokinetics in children with those in adults.
  • To inform potential dose adjustments for pediatric busulfan therapy.

Main Methods:

  • Oral busulfan doses of 1 or 2 mg/kg were administered to children (2 months to 3.6 years).
  • Gas chromatographic assay was used to measure busulfan concentrations.
  • Pharmacokinetic parameters including peak concentration, half-life, AUC, volume of distribution, and clearance were calculated.

Main Results:

  • Pediatric peak busulfan concentrations (1.4–5.2 μmol/L) were lower than in adults.
  • Elimination half-life was slightly faster in children (92 min) compared to adults (140 min).
  • Area under the curve was substantially lower in children, with higher volume of distribution and twice the clearance rate normalized to surface area.

Conclusions:

  • Busulfan disposition in children differs markedly from adults, characterized by lower drug exposure and higher clearance.
  • These pharmacokinetic differences may stem from altered bioavailability or volume of distribution.
  • Separate phase I dose escalation studies with pharmacokinetic assessments are necessary for pediatric busulfan therapy.

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