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Population Pharmacokinetics and Pharmacokinetic-Pharmacodynamic Relationships for Docetaxel

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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.

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Authors and Affiliations

  1. Drug Metabolism and Pharmacokinetics, Aventis Pharma Recherche et Developpement, Antony, France

    René Bruno, Nicole Vivier, Christine Veyrat-Follet, Guy Montay & Gerald R. Rhodes

  2. Collegeville, PA

    René Bruno, Nicole Vivier, Christine Veyrat-Follet, Guy Montay & Gerald R. Rhodes

Authors
  1. René Bruno
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  2. Nicole Vivier
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  3. Christine Veyrat-Follet
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  4. Guy Montay
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  5. Gerald R. Rhodes
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Bruno, R., Vivier, N., Veyrat-Follet, C. et al. Population Pharmacokinetics and Pharmacokinetic-Pharmacodynamic Relationships for Docetaxel. Invest New Drugs 19, 163–169 (2001). https://doi.org/10.1023/A:1010687017717

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