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 pharmacokinetic 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 volume of distribution varied between 0.26 and 1.48 1 kg-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 2.51 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 cyclophosphamide half-life (P < 0.001 in both cases). 6. Dose and concurrent treatment may influence cyclophosphamide metabolism in vivo and thus potentially alter the drugs therapeutic effect.
Yule
S M
SM
Department of Child Health, University of Newcastle upon Tyne, UK.
Boddy
A V
AV
Cole
M
M
Price
L
L
Wyllie
R
R
Tasso
M J
MJ
Pearson
A D
AD
Idle
J R
JR
D000293:Adolescent; D000367:Age Factors; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide