The pharmacokinetics and metabolism of ifosfamide during bolus and infusional administration: a randomized cross-over study

Abstract

In a randomized cross-over trial, 11 patients received ifosfamide (IFOS) in 21-day cycles, which alternated between 3 g m(-2) x (2 or 3) days given as a 1-h bolus doses, or the same total dose as a continuous infusion. Patients who received four or more cycles also alternated between two cycles on dexamethasone 4 mg 8 hourly for 3 days starting 8 h before IFOS, and two cycles off dexamethasone. A total of 34 patient cycles were studied and serum and urinary levels of IFOS, 2 dechloroethylifosfamide (2DC), 3 dechloroethylifosfamide (3DC), carboxyifosfamide (CX) and isophosphoramide mustard (IPM) were measured by thin-layer chromatography. No significant differences could be detected in the areas under the curve (AUCs) of serum concentration, nor in the proportion of IFOS or its metabolites found in the urine. There was no significant effect of dexamethasone on IFOS metabolism. These results indicate that there is no identifiable pharmacokinetic basis for insistence on either bolus or infusional methods of IFOS administration.