title: Significant effect of age on docetaxel pharmacokinetics in Japanese female breast cancer patients by using the population modeling approach.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Clinical Pharmacy and Education, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.|Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Onoue
authors.affiliation: Department of Clinical Pharmacy and Education, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan. iyano@kuhp.kyoto-u.ac.jp.|Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan. iyano@kuhp.kyoto-u.ac.jp.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yano
authors.affiliation: Department of Clinical Pharmacy and Education, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.|Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of Clinical Pharmacy and Education, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.|Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Itohara
authors.affiliation: Departmant of Human Sciences, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hanai
authors.affiliation: Department of Target Therapy Oncology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishiguro
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Motohashi
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Matsubara
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044466:Asian People; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D043823:Taxoids / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel
keywords: Breast cancer; Docetaxel; Female hormone; Pharmacogenetics; Population pharmacokinetics