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Invest New Drugs. 2001 May;19(2):163-9.

Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships for docetaxel.

Author information

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

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.

PMID:
11392450
[Indexed for MEDLINE]

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