Cancer Chemotherapy and Pharmacology

, Volume 32, Issue 6, pp 482–486 | Cite as

A limited sampling model for the pharmacokinetics of etoposide given orally

  • Donatella Gentili
  • Massimo Zucchetti
  • Valter Torri
  • Cristiana Sessa
  • Jolanda de Jong
  • Franco Cavalli
  • Maurizio D'Incalci
Original Articles Etoposide, Pharmacokinetics, Oral Treatment


A limited sampling model of etoposide after oral administration to estimate the area under the plasma concentration-time curve from 0 to 24 h (AUC) by determination of the drug plasma levels at only two time points was developed by a multiple regression analysis on a training data set of 15 patients receiving oral doses ranging from 54 to 90 mg/m2. The equation describing the model is AUC (μg ml−1 h)=5.183 (μg ml−1 h)+1.193 (h)×C1h (μg/ml)+8.439 (h)×C4h (μg/ml) (R2=0.93,P=0.0001), whereC 1h andC 4h represent the plasma etoposide concentrations at 1 and 4 h, respectively. The model was validated prospectively on a test data set of 13 patients receiving oral doses ranging from 52 to 87 mg/m2 and, additionally, on a data set of 7 patients receiving oral doses ranging between 176 and 200 mg/m2, investigated in a previous study. Validation on both test data sets gave a relative mean predictive error of 0.1% and a relative root mean square error of 15.8% and 16.7%, respectively. The present study shows that it is possible to obtain a good estimate of the plasma AUC after oral administration of etoposide using a two-time-point sampling model. The model can be used to monitor the etoposide AUC in patients receiving chronic oral treatment.


Oral Administration Training Data Oral Dose Multiple Regression Analysis Etoposide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Donatella Gentili
    • 1
  • Massimo Zucchetti
    • 1
    • 2
  • Valter Torri
    • 1
  • Cristiana Sessa
    • 2
  • Jolanda de Jong
    • 2
  • Franco Cavalli
    • 2
  • Maurizio D'Incalci
    • 2
  1. 1.Mario Negri Institute for Pharmacological ResearchMilanItaly
  2. 2.Division of OncologyOspedale San GiovanniBellinzonaSwitzerland

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