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Population pharmacokinetics of high-dose etoposide in children receiving different conditioning regimens

Gudrun Würthwein1, Thomas Klingebiel, Sebastian Krümpelmann

  • 1Department of Pediatric Hematology and Oncology, University Hospital Münster, 48129 Münster, Germany.

Anti-Cancer Drugs
|March 27, 2002
PubMed

Insights

High-dose etoposide (Eto) pharmacokinetics in pediatric bone marrow transplant patients showed a three-compartment model with low clearance. Etoposide

Area of Science:

  • Pharmacology
  • Oncology
  • Pediatrics

Background:

  • High-dose etoposide (Eto) is used in conditioning regimens for bone marrow transplantation.
  • Understanding Eto pharmacokinetics is crucial for optimizing treatment and minimizing toxicity in pediatric patients.

Purpose of the Study:

  • To characterize the population pharmacokinetics of high-dose etoposide in children and young adults undergoing bone marrow transplantation.
  • To establish a pharmacokinetic model and determine key parameters like clearance and unbound fraction.

Main Methods:

  • Population pharmacokinetic analysis of etoposide in 31 pediatric patients.
  • Data collected from blood samples up to 97 hours post-infusion.
  • A three-compartment model was used to describe the data.

Main Results:

  • The pharmacokinetic data were best described by a three-compartment model.
  • Etoposide clearance was found to be at the lower range of reported values.
  • High intra-individual variability in the unbound fraction of etoposide was observed.

Conclusions:

  • The established pharmacokinetic model provides insights into etoposide disposition in pediatric transplant patients.
  • Further investigation is needed to determine if children have intrinsically lower etoposide clearance compared to adults after high-dose treatment.

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