Etoposide pharmacokinetics in children: the development and prospective validation of a dosing equation

Cancer Res. 1993 Oct 15;53(20):4881-9.


Pharmacokinetic studies of etoposide administered at 100-200 mg/m2 to 33 children are described. Twenty-seven studies were performed in children aged < 10 years. Repeat studies were performed in 11 patients. Median pharmacokinetic parameters were as follows: plasma clearance, 26 ml/min/m2; volume of distribution, 4.9 liters/m2; area under the etoposide plasma concentration-time curve (AUC), 3.9 mg/ml x min per 100 mg/m2. Interindividual variability in pharmacokinetic parameters was large (coefficient of variation (CV) = 30, 28, and 27%, respectively) in comparison with intraindividual variability (CV = 12, 14, and 12%, respectively). Variability in AUC was much greater in those patients treated with 150-200 mg/m2 etoposide than with 100 mg/m2 (CV, 35 versus 13%) and was related to variability in renal function and prior exposure to cisplatin. Data from the first 20 studies were used to develop pharmacokinetic monitoring equations which were validated in a further 13 patients. The most accurate equation relies upon the elimination constant of 51Cr-EDTA and a single blood specimen taken at the end of the etoposide infusion. [formula: see text] where K = 51Cr-EDTA elimination rate constant. This equation showed no significant bias, and the predictive error was small with respect to AUC calculated according to a two-compartment model. Predictive error did not increase with increasing AUC, whereas a marked increase in predictive error was seen for dosing according to body surface area. Dosing according to body surface area alone led to marked over- or underexposure to etoposide in 8 patients. Pharmacokinetic monitoring using the equation described would have identified these patients and permitted dose modification. This approach provides an accurate means of monitoring etoposide AUC for administration times of 1-4 h without the need for detailed pharmacokinetic sampling. It will allow a significant reduction in the variability of exposure seen with surface area-based dosing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Brain Neoplasms / drug therapy
  • Child
  • Child, Preschool
  • Etoposide / blood
  • Etoposide / pharmacokinetics*
  • Etoposide / therapeutic use*
  • Female
  • Humans
  • Infant
  • Male
  • Metabolic Clearance Rate
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • Neuroblastoma / drug therapy
  • Pineal Gland
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Sarcoma / drug therapy
  • Soft Tissue Neoplasms / drug therapy
  • Teratoma / drug therapy


  • Etoposide