Comparison of continuous infusion and bolus administration of ifosfamide in children

The pharmacological effects of ifosfamide (IFO) are dependent on its metabolism which may vary between different modes of administration. This was studied in 17 patients who received both a continuous infusion (9 g/m2 over 72 h) and repeated bolus administration (3 g/m2 every 24 h for 3 days). Concentrations of IFO and its metabolites were determined in plasma and urine. There was up to 70% less of the dechloroethylated metabolites in plasma following bolus administration compared to continuous infusion. Since dechloroethylation results in the formation of the toxic metabolite chloroacetaldehyde, this difference in metabolism may have an impact on the toxicity of IFO. There were no other consistent differences between the two modes of administration. Auto-induction of IFO metabolism, with an increase in dechloroethylated metabolites, was observed for both modes of administration. In conclusion, apart from dechloroethylation, there is little difference between these two modes of administration. However, during multiple cycles of IFO therapy such differences could have a significant effect.