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 × ULN concomitant with alkaline phosphatase >2.5 × 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.
CITATION STYLE
Bruno, R., Vivier, N., Veyrat-Follet, C., Montay, G., & Rhodes, G. R. (2001). Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships for docetaxel. Investigational New Drugs, 19(2), 163–169. https://doi.org/10.1023/A:1010687017717
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