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Investigational New Drugs

, Volume 19, Issue 2, pp 163–169 | Cite as

Population Pharmacokinetics and Pharmacokinetic-Pharmacodynamic Relationships for Docetaxel

  • René Bruno
  • Nicole Vivier
  • Christine Veyrat-Follet
  • Guy Montay
  • Gerald R. Rhodes
Article

Abstract

The population approach has been implemented prospectively inthe clinical development of docetaxel(Taxotere®). Overall 640 patients were evaluablefor the population PK/PD analysis. The PK analysis evidencedsignificant covariates explaining the inter-patientvariability of docetaxel clearance and the PK/PD analysisdemonstrated that the variability in clearance was asignificant predictor of several safety endpoints. In patientswith clinical chemistry suggestive of mild to moderate liverfunction impairment (SGOT and/or SGPT >1.5 × ULNconcomitant with alkaline phosphatase >2.5 × ULN),total body clearance was lowered by an average of 27%.Specific safety analyses demonstrated that these patients areat a significantly higher risk than others for the developmentof severe docetaxel-induced side effects. Population PK/PDdata were fully integrated into the regulatory dossier and inthe labeling of docetaxel worldwide. Population PK/PD modelsare being used to elaborate a simulation model to predict thesurvival of patients with non-small cell lung cancer treatedwith docetaxel.

docetaxel pharmacokinetics-pharmacodynamics safety efficacy 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • René Bruno
    • 1
    • 2
  • Nicole Vivier
    • 1
    • 2
  • Christine Veyrat-Follet
    • 1
    • 2
  • Guy Montay
    • 1
    • 2
  • Gerald R. Rhodes
    • 1
    • 2
  1. 1.Drug Metabolism and PharmacokineticsAventis Pharma Recherche et DeveloppementAntonyFrance
  2. 2.Collegeville

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