Publié sur : ASCO Annual Meeting Abstract N° 846 - 1998
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Ifosfamide and its main metabolites in children during the first 4 days of a continuous infusion
B Gourmel, S Denis, B Bousquet, G Delepine, Nicole Delepine

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Ifosfamide and its main metabolites in children during the first 4 days of a continuous infusion

Developmental Therapeutics - Clinical Pharmacology and Immunotherapy

Abstract:

Forty cures of Ifosfamide (If.) were administered to 14 children, aged 2 to 19 years.
The dose regimen was 3g/m[Superscript 2]/day during 4 to 7 days. Auto-induction of the parent compound has been previously described in such administration conditions. A new gas-chromatography method, allowing simultaneous determination of If. and its main metabolites, either inactive 2 and 3 dechloroethyl If. (2dIf.,3dIf.) or active 4 hydroxy If.(4OHIf.), enabled us to estimate the real impact of this process on drug metabolism and metabolite production.
Data were estimated between the 1st and the 4th days. To compare inter-patient results, data were expressed in grams of If. infused per day. The table summarizes the mean values and the SD of the concentrations ([Mu]g/ml) and of the areas under curve ([Mu]g*h/ml).
Despite large inter-individual variations, similar curve features were noted for each patient. Concerning the If conc. it is clear that a continuous decrease (49.7%) was observed related to induction whereas 2dIf. and 3dIf. reached max conc. on day 2 and then decreased slightly. At the same time 4OHIf increased (29.7%). Concerning A.U.C, If. value was max at 24--48h and then decreased (16.8%).
Metabolite data at this time still remained constant or decreasing for 2dIf. Maximum 4OHIf production was reached at 48--72h. These data suggest that, despite induction of the parent compound, inactive metabolism seemed to be saturable from day 2 even when the active one increased slightly.
Nevertheless, as 4OHIf is the sole component able to enter the cell, its production could be greater than observed.

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