Population pharmacokinetics of docetaxel in patients with hepatic dysfunction treated in an oncology practice

Hironobu Minami, Kenji Kawada, Yasutsuna Sasaki, Makoto Tahara, Tadahiko Igarashi, Kuniaki Itoh, Hirofumi Fujii, Toshiaki Saeki, Kazuhiro Ozawa, Hitoshi Sato

研究成果: Article査読

26 被引用数 (Scopus)

抄録

To investigate the relationship between the degree of liver dysfunction and the pharmacokinetics of docetaxel, a population pharmacokinetic model was developed in an oncology practice without excluding patients with moderate to severe liver dysfunction. Two hundred patients were treated with docetaxel as a single agent or in combination chemotherapy. The plasma concentration-time course data were analyzed using a three-compartment open model with zero-order administration and first-order elimination on the NONMEM program. Sixty-one had elevated transaminase levels, and alkaline phosphatase was elevated in 40. Body surface area, albumin, α1-acid glycoprotein, and liver function were found to be significant covariates for the systemic clearance of docetaxel. Compared to patients with normal or minimal impairment of liver function, patients with grade 2 and 3 elevations of transaminases at baseline in conjunction with elevation of alkaline phosphatase had 22 and 38% lower clearances, respectively. Goodness-of-fit plots indicated that the model was fitted well with the observed data, and the bootstrap method guaranteed robustness of the model. We developed a population pharmacokinetic model for docetaxel, which can be used in the setting of an oncology practice. Based on the model, dose reduction by approximately 20 and 40% should be considered for patients with grade 2 and 3 elevations of transaminases at baseline in conjunction with elevation of alkaline phosphatase, respectively.

本文言語English
ページ(範囲)144-149
ページ数6
ジャーナルCancer science
100
1
DOI
出版ステータスPublished - 13-01-2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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