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Population pharmacokinetic-based dosing of intravenous busulfan in pediatric patients

Brian P Booth1, Atiqur Rahman, Ramzi Dagher

  • 1Food and Drug Administration, Office of Clinical Pharmacology, Division of Clinical Pharmacology 5, 10903 New Hampshire Avenue, Building 21, Room 3668, Silver Spring, MD 20993-0002, USA.

Journal of Clinical Pharmacology
|December 29, 2006
PubMed

Insights

This study characterized intravenous busulfan pharmacokinetics in pediatric patients. New dosing recommendations aim to improve therapeutic targeting by adjusting for patient weight.

Area of Science:

  • Pharmacology
  • Pediatric Oncology

Background:

  • Busulfan is a critical chemotherapeutic agent used in pediatric conditioning regimens.
  • Optimizing busulfan dosing is essential for maximizing efficacy and minimizing toxicity in pediatric patients.

Purpose of the Study:

  • To characterize the pharmacokinetics (PK) of intravenous busulfan in pediatric patients.
  • To provide evidence-based dosing recommendations for intravenous busulfan in this population.

Main Methods:

  • Twenty-four pediatric patients received intravenous busulfan with dense PK sampling.
  • Pharmacokinetic parameters were analyzed using a 1-compartment model.
  • Monte Carlo simulations were performed to evaluate different dosing strategies.

Main Results:

  • The PK of intravenous busulfan was described by a 1-compartment model with specific clearance and volume of distribution values.
  • Simulations showed that mg/kg and mg/m2 dosing regimens achieved target exposure in approximately 60% of patients.
  • The model suggests distinct dosing for patients <= 12 kg (1.1 mg/kg) versus > 12 kg (0.8 mg/kg).

Conclusions:

  • The developed PK model provides a basis for refined intravenous busulfan dosing in pediatric patients.
  • Weight-based dosing adjustments, as proposed, can enhance therapeutic targeting.
  • Incorporating therapeutic drug monitoring alongside dose adjustments is recommended for further optimization.

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