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

Purpose: The pharmacokinetics and metabolism of cyclophosphamide (CPA) when given as a l-h and a 24-h infusion to children were compared. Methods: Thi rteen children with a variety of different malignancies received an identic al dose of cyclophosphamide as a 1- and 24-h infusion. In each case the con centration of CPA and its principal metabolites were measured by a thin-lay er-chromatography-pho to graphic-densitometry technique. Results: Cyclophos phamide clearance was greater during the 24-h infusion, following time-depe ndent increases in the metabolism of the drug (autoinduction) (median 5.1 v s 3.1 1/h/m(2): P=0.037). Autoinduction was seen in five children (38%), pr oducing 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 pr incipal inactive metabolites carboxyphosphamide and dechloroethylcyclophosp hamide. Conclusions: These results suggest potential benefits of prolonging the infusion of CPA in clinical practice.