Cyclophosphamide metabolism in children following a 1-h and a 24-h infusion

Abstract.

Purpose: The pharmacokinetics and metabolism of cyclophosphamide (CPA) when given as a 1-h and a 24-h infusion to children were compared. Methods: Thirteen children with a variety of different malignancies received an identical dose of cyclophosphamide as a 1- and 24-h infusion. In each case the concentration of CPA and its principal metabolites were measured by a thin-layer-chromatography–photographic-densitometry technique. Results: Cyclophosphamide clearance was greater during the 24-h infusion, following time-dependent increases in the metabolism of the drug (autoinduction) (median 5.1 vs 3.1 l/h/m²: P=0.037). Autoinduction was seen in five children (38%), producing a median end of infusion concentration of 49% (range 28–89%) of the maximum and was not accompanied by an increase in the production of the principal inactive metabolites carboxyphosphamide and dechloroethylcyclophosphamide. Conclusions: These results suggest potential benefits of prolonging the infusion of CPA in clinical practice.