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Pharmacokinetics and metabolism of cyclophosphamide in paediatric patients

Lookup NU author(s): Professor Alan Boddy, Professor Andrew Pearson

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Abstract

The pharmacokinetics and metabolism of cyclophosphamide were studied in nine paediatric patients. Plasma samples were obtained from eight subjects and urine was collected from six children during a 24-h period after drug administration. Cyclophosphamide and its major metabolites phosphoramide mustard (PM), carboxyphosphamide (CX), dechloroethylcyclophosphamide (DCCP) and 4-ketocyclophosphamide (KETO) were determined in plasma and urine using high-performance thin-layer chromatography-photographic densitometry (HPTLC-PD). Cyclophosphamide (CP) was nearly, if not completely, cleared from plasma by 24 h after its administration. The plasma half-life of CP ranged from 2.15 to 8.15 h; it decreased following higher doses and was shorter than that previously reported for adult patients. Both the apparent volume of distribution (0.49 +/- 1.4 l/kg) and the total body clearance (2.14 +/- 1.4 1 m-2 h-1) increased with increasing dose. Renal clearance ranged between 0.12 and 0.58 l/h (mean, 0.43 +/- 0.19 l/h). Between 5.4% and 86.1% of the total delivered dose was recovered as unchanged drug in the urine. The major metabolites identified in plasma and urine were PM and CX. One patient appeared to be deficient in CX formation. This study suggests that there is interpatient variability in the pharmacokinetics and metabolism of CP in paediatric patients. The shorter half-life and higher clearance as compared with adult values indicate faster CP metabolism in children.


Publication metadata

Author(s): Tasso, M. J., Boddy, A. V., Price, L., Wyllie, R. A., Pearson, A. D. J., Idle, J. R.

Publication type: Article

Publication status: Published

Journal: Cancer Chemotherapy and Pharmacology

Year: 1992

Volume: 30

Issue: 3

Pages: 207-211

Print publication date: 01/05/1992

ISSN (print): 0344-5704

ISSN (electronic): 1432-0843

URL: http://dx.doi.org/10.1007/BF00686313

DOI: 10.1007/BF00686313


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