Cyclophosphamide pharmacokinetics in children

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Abstract
1 Cyclophosphamide pharmacokinetics were measured in 38 children with cancer.2 A high degree of inter‐patient variation was seen in all pharmacokinetic parameters. Cyclophosphamide half‐life varied between 1.1 and 16.8 h, clearance varied between 1.2 and 10.61 h‐1m‐2and volume of distribution varied between 0.26 and 1.48 1kg‐1.3 The half–life of cyclophosphamide was prolonged at high dose levels (P = 0.008).4 Children who had received prior treatment with dexamethasone showed a mean increase in clearance of 2.5 1 h‐1m‐2(P= 0.001) presumably as a result of CYP450 enzyme induction.5 Treatment with allopurinol or chlorpromazine was associated with a significant increase in cyclophosphamide half‐life (P< 0.001 in both cases).6 Dose and concurrent treatment may influence cyclophosphamide metabolismin vivoand thus potentially alter the drugs therapeutic effect.