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Cyclophosphamide metabolism in children following a 1-h and a 24-h infusion
1Roche Products Ltd, 40 Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AY, UK. murray.yule@roche.com
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.