Population pharmacokinetic and pharmacodynamic analysis for time courses of docetaxel-induced neutropenia in Japanese cancer patients.
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.
Ozawa
Kazuhiro
K
Department of Clinical and Molecular Pharmacokinetics/Pharmacodynamics, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Minami
Hironobu
H
Sato
Hitoshi
H
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000077143:Docetaxel; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan; D007700:Kinetics; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced*; D015203:Reproducibility of Results; D043823:Taxoids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel