Population pharmacokinetics of etoposide: application to therapeutic drug monitoring

Ther Drug Monit. 2002 Dec;24(6):709-14. doi: 10.1097/00007691-200212000-00005.

Abstract

Antineoplastic agent etoposide (VP16) displays narrow therapeutic index and erratic pharmacokinetics, and dose individualization is a convenient way for overcoming the interpatient variability, so as to maintain the drug exposure within a therapeutic range. The authors proposed a population-based Bayesian methodology to adjust routinely VP16 dosage when given as a 5-day infusion. The mean VP16 pharmacokinetic parameters of the reference population calculated from 14 patients following the two-stage method were CL = 1.92 +/- 0.512 L/h and t(1/2) = 6.7 +/- 2 hours. The reference population was next used prospectively for Bayesian dose individualization for 25 patients (47 courses) undergoing 5-day infusions of VP16. Resulting steady-state concentrations proved to be successfully adjusted to the target values in 77% of the courses. Therefore, the method presented here meets the requirements for routine therapeutic drug monitoring of VP16, a major anticancer drug extensively used in clinical oncology.

Publication types

  • Validation Study

MeSH terms

  • Adult
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Bayes Theorem
  • Chromatography, High Pressure Liquid
  • Drug Monitoring / methods*
  • Etoposide / administration & dosage
  • Etoposide / pharmacokinetics*
  • Female
  • Half-Life
  • Humans
  • Male
  • Middle Aged
  • Population
  • Spectrometry, Fluorescence

Substances

  • Antineoplastic Agents, Phytogenic
  • Etoposide