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Pharmacokinetics of PEGasparaginase in Infants with Acute Lymphoblastic Leukemia

Leiah J Brigitha1,2, Veerle Mondelaers3, Yiwei Liu4

  • 1Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, Netherlands.

Pharmaceutical Research
|March 28, 2024
PubMed

Insights

The pharmacokinetics of PEGasparaginase in infants with acute lymphoblastic leukemia (ALL) are similar to older children. A recommended dose of 1,500 IU/m² is suggested for infants, with therapeutic drug monitoring for optimal treatment.

Area of Science:

  • Pharmacology
  • Pediatric Oncology
  • Pharmacokinetics

Background:

  • PEGasparaginase is crucial for treating pediatric acute lymphoblastic leukemia (ALL).
  • Optimal dosing for infants under one year with ALL lacks sufficient evidence.
  • This study investigates PEGasparaginase pharmacokinetics in infants with newly diagnosed ALL.

Purpose of the Study:

  • To determine the pharmacokinetics of PEGasparaginase in infants with newly diagnosed ALL.
  • To provide insights into PEGasparaginase clearance and dosing for this specific population.
  • To establish evidence-based dosing recommendations for infants with ALL.

Main Methods:

  • Population pharmacokinetic assessment using non-linear mixed effects modeling (NONMEM).
  • Inclusion of 68 infants with ALL and 388 asparaginase activity samples.
  • Utilized a one-compartment model with time-dependent clearance.

Main Results:

  • Body weight significantly correlated with clearance and volume of distribution.
  • Estimated half-life decreased from 11.7 days post-administration to 1.8 days after 14 days.
  • Clearance was 19.5% lower in the post-induction phase compared to induction.

Conclusions:

  • Infant PEGasparaginase pharmacokinetics are comparable to older children (1-18 years).
  • Recommended PEGasparaginase dose for infants is 1,500 IU/m² without age-specific adaptations.
  • Therapeutic drug monitoring is recommended as standard practice for infants with ALL.
Abstract

Keywords:
PEgasparaginaseacute lymphoblastic leukemiainfantpopulation pharmacokinetics

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