Population pharmacokinetics and exploratory pharmacodynamics of ifosfamide according to continuous or short infusion schedules: an n = 1 randomized study

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

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 β₂‐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.

DOI: 10.1111/j.1365-2125.2007.03095.x

View this article

• Full article (html)
• Enhanced article (html)
• PDF
• References