Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships for docetaxel

Invest New Drugs. 2001 May;19(2):163-9. doi: 10.1023/a:1010687017717.

Abstract

The population approach has been implemented prospectively in the clinical development of docetaxel (Taxotere). Overall 640 patients were evaluable for the population PK/PD analysis. The PK analysis evidenced significant covariates explaining the inter-patient variability of docetaxel clearance and the PK/PD analysis demonstrated that the variability in clearance was a significant predictor of several safety endpoints. In patients with clinical chemistry suggestive of mild to moderate liver function impairment (SGOT and/or SGPT > 1.5 x ULN concomitant with alkaline phosphatase >2.5 x ULN), total body clearance was lowered by an average of 27%. Specific safety analyses demonstrated that these patients are at a significantly higher risk than others for the development of severe docetaxel-induced side effects. Population PK/PD data were fully integrated into the regulatory dossier and in the labeling of docetaxel worldwide. Population PK/PD models are being used to elaborate a simulation model to predict the survival of patients with non-small cell lung cancer treated with docetaxel.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / drug therapy
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Clinical Trials as Topic
  • Computer Simulation
  • Docetaxel
  • Humans
  • Lung Neoplasms / drug therapy
  • Models, Statistical
  • Neoplasms / drug therapy
  • Nonlinear Dynamics
  • Paclitaxel / analogs & derivatives
  • Paclitaxel / pharmacokinetics*
  • Paclitaxel / pharmacology*
  • Prospective Studies
  • Research Design
  • Taxoids*

Substances

  • Antineoplastic Agents, Phytogenic
  • Taxoids
  • Docetaxel
  • Paclitaxel