A limited-sampling strategy to estimate individual pharmacokinetic parameters of vinorelbine in elderly patients with advanced metastatic cancer

Anticancer Drugs. 2002 Jun;13(5):473-80. doi: 10.1097/00001813-200206000-00005.

Abstract

The aim of this study was to characterize the population pharmacokinetic of vinorelbine in elderly patients and to propose a limited-sampling strategy to estimate individual pharmacokinetic parameters. Vinorelbine was administered by a 10-min continuous infusion at a dose of 20-30 mg/m2. The population parameters were computed, using a three-compartment model, from an initial group of 27 patients. Twelve additional courses were used for model validation and evaluation of eight different limited-sampling strategies. The inter-individual variability of CL was explained by a linear dependency with age. The population average parameters and the interindividual variabilities (CV%) were: CL=47.1 l/h (31.7%), V=16.6 l (64%), k21=0.776 h-1 (20%), k31=0.0346 h-1 (15.2%), alpha=0.431 h-1 (6.84%) and beta=0.0167 h-1 (25%). Bayesian estimation with three measured levels (end of infusion, and 6 and 48 h) can be selected, because it allows adequate estimation of CL, elimination half-life and vinorelbine concentrations with a non-significant bias. Moreover, the choice of these three sampling times presents practicality advantages for the patient's comfort. Vinorelbine clearance decreasing with age and AUC being a good predictor of several toxicity end points during vinorelbine treatment, the limited-sampling strategy developed in this paper may be clinically relevant.

MeSH terms

  • Aged
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Area Under Curve
  • Bayes Theorem
  • Humans
  • Metabolic Clearance Rate
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Population
  • Sampling Studies
  • Vinblastine / analogs & derivatives*
  • Vinblastine / pharmacokinetics*
  • Vinorelbine

Substances

  • Antineoplastic Agents, Phytogenic
  • Vinblastine
  • Vinorelbine