Population pharmacokinetic and pharmacodynamic analysis for time courses of docetaxel-induced neutropenia in Japanese cancer patients

Cancer Sci. 2007 Dec;98(12):1985-92. doi: 10.1111/j.1349-7006.2007.00615.x. Epub 2007 Sep 19.

Abstract

The present study describes a population pharmacokinetic and pharmacodynamic (PK/PD) analysis based on data obtained from cancer patients treated with docetaxel at the National Cancer Center Hospital East in Japan. Docetaxel was infused intravenously over 1 h every 3 weeks, and time courses of absolute neutrophil counts (ANC) for a total of 395 observations (62 patients) were analyzed using a semimechanistic-physiological PK/PD model in the NONMEM program. The prominent feature of our PK/PD model is that it has the capability to predict a temporary increase in ANC. Among 10 patient factors, alpha(1)-acid glycoprotein was selected as a significant covariate for drug effect as the increase in alpha(1)-acid glycoprotein was negatively correlated with the drug effect. Goodness-of-fit plots indicated that the model fitted well with the observed data, and the bootstrap method guaranteed robustness of the model. In conclusion, we developed a novel population PK/PD model that can adequately analyze ANC profiles after docetaxel administration in oncology practice, where temporary but consistent increases in ANC were observed.

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / toxicity*
  • Docetaxel
  • Humans
  • Infusions, Intravenous
  • Japan
  • Kinetics
  • Models, Biological
  • Neoplasms / drug therapy*
  • Neutropenia / chemically induced*
  • Reproducibility of Results
  • Taxoids / administration & dosage
  • Taxoids / blood
  • Taxoids / pharmacokinetics*
  • Taxoids / toxicity*

Substances

  • Antineoplastic Agents
  • Taxoids
  • Docetaxel