Cyclophosphamide Metabolism in Children 1

  • Pars DexA Mes, Flu MesD 1871 Cotrim, +7 authors Dcx PhyA Mes
  • Published 2006

Abstract

The alkylating agentcyclophosphamideis a prodrug which is metabo lized in vivo to produce both therapeutic and toxic effects.Cyclophosph amide metabolism was Investigated in 36 children with various malignan des. Concentrations of cyclophosphamide and Its principal metabolites were measured In plasma and urine using a quantitative bigh-perfor mance ThC method. The results Indicated a high degree of Inter-patient variationin metabolism. In contrastto previousadultstudieson urinary metabolites,plasmacarboxyphosphamideconcentrationsdid not support the existenceof polymorphic metabolism. Plasma concentrationsof de chlorethylcyclophosphamldeand carboxyphosphamidewerecorrelated in individual patients, suggesting that the activity of both aldehyde dehydro genaseand cytochrome P450enzyme(s)determine carboxyphosphamide production in vivo. The presence of ketocyclophosphamide In plasma was strongly associated with dexainethasone pretreatment and was also ac companiedby a high clearanceofthe parent drug. Interpatlent differences In metabolism reflect Individual levels of enzyme expression and may contribute to variation In clinical effect.

3 Figures and Tables

Cite this paper

@inproceedings{Mes2006CyclophosphamideMI, title={Cyclophosphamide Metabolism in Children 1}, author={Pars DexA Mes and Flu MesD 1871 Cotrim and Prop Vcr PhyA Mes Hyr and D T Thio and DcxA Mes and Mes Imip TeicA Doxo and Ran Acy ES 2000 Flu and DcxD Mes and PNET 1500 Vcr and Dcx PhyA Mes}, year={2006} }