CYCLOPHOSPHAMIDE PHARMACOKINETICS IN CHILDREN

1 Cyclophosphamide pharmacokinetics were measured in 38 children with cancer. 2 A high degree of inter-patient variation was seen in all pha rmacokinetic parameters. Cyclophosphamide half-life varied between 1.1 . and 16.8 h, clearance varied between 1.2 and 10.61 h(-1)m(-2) and vo lume of distribution varied between 0.26 and 1.48 1kg(-1) 3 The half-l ife 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 2.51 h(-1) m(-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 cyclop hosphamide half-life (P < 0.001 in both cases). 6 Dose and concurrent treatment may in fluence cyclophosphamide metabolism in vivo and thus potentially alter the drugs therapeutic effect.