Cyclophosphamide metabolism in children following a 1-h and a 24-h infusion.
OBJECTIVE
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.
Yule
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Roche Products Ltd, 40 Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AY, UK. murray.yule@roche.com
Price
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Cole
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Pearson
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Boddy
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D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D002855:Chromatography, Thin Layer; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D003720:Densitometry; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000188:drug therapy; D018709:Statistics, Nonparametric
D003520:Cyclophosphamide