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Updated: Jun 11, 2026

A Human Peripheral Blood Mononuclear Cell (PBMC) Engrafted Humanized Xenograft Model for Translational Immuno-oncology (I-O) Research
Published on: August 15, 2019
Population pharmacokinetics and exploratory pharmacodynamics of ifosfamide according to continuous or short infusion
Etienne G C Brain1, Kevan Rezai, François Lokiec
1Department of Medical Oncology, René Huguenin Cancer Centre, 35, rue Dailly, 92210 Saint-Cloud, France. e.brain@stcloud-huguenin.org
What Is Already Known About This Subject:
* The optimal infusion duration for ifosfamide remains to be determined. * No differences according to time of infusion have been identified in traditional pharmacokinetic endpoints, such as area under the curve. * The impact on pharmacodynamics has never been modelled or correlated with pharmacokinetics.
What This Study Adds:
* The pharmacokinetics and pharmacodynamics of ifosfamide and its main metabolites can both be modelled with no influence of infusion duration. * Pharmacodynamic modelling (renal and haematological toxicity) allows further simulations of new schedules with favourable toxicity profiles.
Aims:
To model the pharmacokinetics and pharmacodynamics of ifosfamide and its key metabolites. The pharmacodynamic parameters included were renal toxicity and myelosuppression measured using urinary beta(2)-microglobulin (BMG) and absolute neutrophil count (ANC), respectively.
Methods:
Seventeen patients were enrolled into an n = 1 randomized trial during two consecutive cycles of ifosfamide 9 g m(-2) during each cycle given by a 3 h or 72 h infusion. Data were analyzed using NONMEM.
Results:
Ifosfamide and metabolite concentration-time profiles were described by a one-compartment open-model with auto-induction of clearance. BMG and ANC time-courses were related to ifosfamide concentration via indirect response models.
Conclusions:
This modelling allowed the simulation of weekly schedules of flat doses with favourable myelotoxic profiles.
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