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Updated: Jun 30, 2025

Modeling Chemotherapy Resistant Leukemia In Vitro
Published on: February 9, 2016
Proof of concept of physiologically based pharmacokinetic modelling in paediatric acute lymphoblastic leukaemia
1Department of Clinical Pharmacy, Institute for Pharmaceutical and Medical Chemistry, University of Münster, Münster, Germany.
Abstract:
Physiologically based pharmacokinetic (PBPK) modelling is an alternative modelling technique that is increasingly used in pharmacokinetics. Due to its nature, it can be complementarily employed to population pharmacokinetics, especially when it comes to small population size. Here, we report the proof of concept of its application to accurately describe the pharmacokinetics of a recombinant L-asparaginase in paediatric patients with acute lymphoblastic leukaemia. Data from two randomized, double-blind, phase II/III clinical studies (MC-ASP.4/ALL; MC-ASP.5/ALL) were included to setup and evaluate the final model, respectively. Final population values for basic pharmacokinetic parameters were calculated (clearance: 0.0569 L/h/19.5 kg, volume of distribution: 1.251 L, half-life: 18.5 h, trough concentration: 140.9 IU/L). Pharmacokinetic parameter prediction as well as predictive performance of the model proofed to be comparable to a separately developed population pharmacokinetic model with 13% deviation in predicted median L-asparaginase trough levels. To the best of our knowledge, this is the first whole-body PBPK model of a non-antibody therapeutic protein.
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