Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships for docetaxel.

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.

journal_name

Invest New Drugs

authors

Bruno R,Vivier N,Veyrat-Follet C,Montay G,Rhodes GR

doi

10.1023/a:1010687017717

subject

Has Abstract

pub_date

2001-05-01 00:00:00

pages

163-9

issue

2

eissn

0167-6997

issn

1573-0646

journal_volume

19

pub_type

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