Significant effect of age on docetaxel pharmacokinetics in Japanese female breast cancer patients by using the population modeling approach

Haruka Onoue, Ikuko Yano, Atsuko Tanaka, Kotaro Itohara, Akiko Hanai, Hiroshi Ishiguro, Hideyuki Motohashi, Satohiro Masuda, Kazuo Matsubara

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: Docetaxel is frequently used in the treatment of a wide variety of solid tumors, including breast cancer. The aim of this study is to obtain the population pharmacokinetic parameters of docetaxel in Japanese female patients with breast cancer. Methods: Blood samples from 24 patients were collected sequentially before and after docetaxel infusion. Genomic DNA was isolated from the peripheral blood and genotyped for the selected polymorphisms in the candidate genes of drug transporters and metabolizing enzymes. The influence of patient characteristics on the pharmacokinetics of docetaxel was evaluated using the nonlinear-mixed-effect modeling program, NONMEM. As a basis for comparison, the pharmacokinetics of another taxane paclitaxel in 41 separate female patients with breast cancer was calculated. Results: A two-compartment model adequately described the pharmacokinetic profiles of docetaxel. The population mean estimates of the total body clearance for patients aged 58 years or less and the central volume of distribution for docetaxel were 32.6 L/h and 5.77 L, respectively. In patients over 58 years, the clearance was 24 % higher than that in the younger patients. No influences of the genotypes examined were noted on the clearance of docetaxel. The clearance of paclitaxel was not affected by patient age. Conclusions: Patients over the age of 58 years showed significantly higher clearance of docetaxel than that in patients aged 58 years or less. Since the clearance of paclitaxel was not affected by the age, it is possible that the pharmacokinetic mechanisms of docetaxel might be specifically affected by age in females.

Original languageEnglish
Pages (from-to)703-710
Number of pages8
JournalEuropean Journal of Clinical Pharmacology
Volume72
Issue number6
DOIs
Publication statusPublished - Jan 1 2016

Fingerprint

docetaxel
Pharmacokinetics
Breast Neoplasms
Population
Paclitaxel

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Significant effect of age on docetaxel pharmacokinetics in Japanese female breast cancer patients by using the population modeling approach. / Onoue, Haruka; Yano, Ikuko; Tanaka, Atsuko; Itohara, Kotaro; Hanai, Akiko; Ishiguro, Hiroshi; Motohashi, Hideyuki; Masuda, Satohiro; Matsubara, Kazuo.

In: European Journal of Clinical Pharmacology, Vol. 72, No. 6, 01.01.2016, p. 703-710.

Research output: Contribution to journalArticle

Onoue, Haruka ; Yano, Ikuko ; Tanaka, Atsuko ; Itohara, Kotaro ; Hanai, Akiko ; Ishiguro, Hiroshi ; Motohashi, Hideyuki ; Masuda, Satohiro ; Matsubara, Kazuo. / Significant effect of age on docetaxel pharmacokinetics in Japanese female breast cancer patients by using the population modeling approach. In: European Journal of Clinical Pharmacology. 2016 ; Vol. 72, No. 6. pp. 703-710.
@article{1590acfa06214effacf4b75d6828f064,
title = "Significant effect of age on docetaxel pharmacokinetics in Japanese female breast cancer patients by using the population modeling approach",
abstract = "Purpose: Docetaxel is frequently used in the treatment of a wide variety of solid tumors, including breast cancer. The aim of this study is to obtain the population pharmacokinetic parameters of docetaxel in Japanese female patients with breast cancer. Methods: Blood samples from 24 patients were collected sequentially before and after docetaxel infusion. Genomic DNA was isolated from the peripheral blood and genotyped for the selected polymorphisms in the candidate genes of drug transporters and metabolizing enzymes. The influence of patient characteristics on the pharmacokinetics of docetaxel was evaluated using the nonlinear-mixed-effect modeling program, NONMEM. As a basis for comparison, the pharmacokinetics of another taxane paclitaxel in 41 separate female patients with breast cancer was calculated. Results: A two-compartment model adequately described the pharmacokinetic profiles of docetaxel. The population mean estimates of the total body clearance for patients aged 58 years or less and the central volume of distribution for docetaxel were 32.6 L/h and 5.77 L, respectively. In patients over 58 years, the clearance was 24 {\%} higher than that in the younger patients. No influences of the genotypes examined were noted on the clearance of docetaxel. The clearance of paclitaxel was not affected by patient age. Conclusions: Patients over the age of 58 years showed significantly higher clearance of docetaxel than that in patients aged 58 years or less. Since the clearance of paclitaxel was not affected by the age, it is possible that the pharmacokinetic mechanisms of docetaxel might be specifically affected by age in females.",
author = "Haruka Onoue and Ikuko Yano and Atsuko Tanaka and Kotaro Itohara and Akiko Hanai and Hiroshi Ishiguro and Hideyuki Motohashi and Satohiro Masuda and Kazuo Matsubara",
year = "2016",
month = "1",
day = "1",
doi = "10.1007/s00228-016-2031-3",
language = "English",
volume = "72",
pages = "703--710",
journal = "European Journal of Clinical Pharmacology",
issn = "0031-6970",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - Significant effect of age on docetaxel pharmacokinetics in Japanese female breast cancer patients by using the population modeling approach

AU - Onoue, Haruka

AU - Yano, Ikuko

AU - Tanaka, Atsuko

AU - Itohara, Kotaro

AU - Hanai, Akiko

AU - Ishiguro, Hiroshi

AU - Motohashi, Hideyuki

AU - Masuda, Satohiro

AU - Matsubara, Kazuo

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Purpose: Docetaxel is frequently used in the treatment of a wide variety of solid tumors, including breast cancer. The aim of this study is to obtain the population pharmacokinetic parameters of docetaxel in Japanese female patients with breast cancer. Methods: Blood samples from 24 patients were collected sequentially before and after docetaxel infusion. Genomic DNA was isolated from the peripheral blood and genotyped for the selected polymorphisms in the candidate genes of drug transporters and metabolizing enzymes. The influence of patient characteristics on the pharmacokinetics of docetaxel was evaluated using the nonlinear-mixed-effect modeling program, NONMEM. As a basis for comparison, the pharmacokinetics of another taxane paclitaxel in 41 separate female patients with breast cancer was calculated. Results: A two-compartment model adequately described the pharmacokinetic profiles of docetaxel. The population mean estimates of the total body clearance for patients aged 58 years or less and the central volume of distribution for docetaxel were 32.6 L/h and 5.77 L, respectively. In patients over 58 years, the clearance was 24 % higher than that in the younger patients. No influences of the genotypes examined were noted on the clearance of docetaxel. The clearance of paclitaxel was not affected by patient age. Conclusions: Patients over the age of 58 years showed significantly higher clearance of docetaxel than that in patients aged 58 years or less. Since the clearance of paclitaxel was not affected by the age, it is possible that the pharmacokinetic mechanisms of docetaxel might be specifically affected by age in females.

AB - Purpose: Docetaxel is frequently used in the treatment of a wide variety of solid tumors, including breast cancer. The aim of this study is to obtain the population pharmacokinetic parameters of docetaxel in Japanese female patients with breast cancer. Methods: Blood samples from 24 patients were collected sequentially before and after docetaxel infusion. Genomic DNA was isolated from the peripheral blood and genotyped for the selected polymorphisms in the candidate genes of drug transporters and metabolizing enzymes. The influence of patient characteristics on the pharmacokinetics of docetaxel was evaluated using the nonlinear-mixed-effect modeling program, NONMEM. As a basis for comparison, the pharmacokinetics of another taxane paclitaxel in 41 separate female patients with breast cancer was calculated. Results: A two-compartment model adequately described the pharmacokinetic profiles of docetaxel. The population mean estimates of the total body clearance for patients aged 58 years or less and the central volume of distribution for docetaxel were 32.6 L/h and 5.77 L, respectively. In patients over 58 years, the clearance was 24 % higher than that in the younger patients. No influences of the genotypes examined were noted on the clearance of docetaxel. The clearance of paclitaxel was not affected by patient age. Conclusions: Patients over the age of 58 years showed significantly higher clearance of docetaxel than that in patients aged 58 years or less. Since the clearance of paclitaxel was not affected by the age, it is possible that the pharmacokinetic mechanisms of docetaxel might be specifically affected by age in females.

UR - http://www.scopus.com/inward/record.url?scp=84959094140&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959094140&partnerID=8YFLogxK

U2 - 10.1007/s00228-016-2031-3

DO - 10.1007/s00228-016-2031-3

M3 - Article

C2 - 26905999

AN - SCOPUS:84959094140

VL - 72

SP - 703

EP - 710

JO - European Journal of Clinical Pharmacology

JF - European Journal of Clinical Pharmacology

SN - 0031-6970

IS - 6

ER -