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Pharmacokinetics of Erwinia asparaginase after intravenous and intramuscular administration

B K Albertsen1, P Jakobsen, H Schrøder

  • 1Department of Pharmacology, University of Aarhus, Denmark. bka@farm.au.dk

Cancer Chemotherapy and Pharmacology
|August 8, 2001
PubMed

Insights

This study determined the pharmacokinetics of Erwinia asparaginase (ASNase) in children with acute lymphoblastic leukemia (ALL). Intramuscular administration showed limited absorption, highlighting the need for pharmacokinetic evaluation before new drug schedules.

Area of Science:

  • Pharmacology
  • Oncology
  • Clinical Pharmacy

Background:

  • Erwinia asparaginase (ASNase) is a crucial chemotherapeutic agent.
  • Understanding its pharmacokinetic profile is essential for optimizing treatment efficacy and safety in acute lymphoblastic leukemia (ALL).

Purpose of the Study:

  • To elucidate the pharmacokinetic parameters of Erwinia asparaginase following intravenous (i.v.) and intramuscular (i.m.) administration.
  • To assess the absorption, distribution, metabolism, and excretion (ADME) characteristics of ASNase in pediatric ALL patients.

Main Methods:

  • A cohort of 29 children with newly diagnosed ALL received Erwinia ASNase (30,000 IU/m2) daily for 10 days during induction therapy.
  • Patients were administered ASNase via i.v. or i.m. routes.
  • Plasma ASNase activity was quantified using a spectrophotometric assay at various time points.

Main Results:

  • The estimated half-life of Erwinia ASNase was 6.4 ± 0.5 hours.
  • Intramuscular administration demonstrated an absorption rate that limited drug elimination.
  • The apparent volume of distribution was comparable to plasma volume, and clearance indicated Erwinia ASNase is a low-clearance drug. Bioavailability after i.m. administration was 27.0 ± 4.5%.

Conclusions:

  • This study provides substantial pharmacokinetic data for Erwinia asparaginase in pediatric ALL patients.
  • The findings underscore the critical importance of rigorous pharmacokinetic assessments before introducing new drugs or altered administration schedules.
Abstract

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