Effect of age and single versus multiple dose pharmacokinetics of letrozole (Femara) in breast cancer patients

Biopharm Drug Dispos. 2001 Jul;22(5):191-7. doi: 10.1002/bdd.273.


Letrozole (trademark Femara) is a new orally active, potent and selective aromatase inhibitor for the hormonal treatment of advanced breast cancer in postmenopausal women. The pharmacokinetics of letrozole and the suppression of peripheral estrogens were studied in 28 breast cancer patients after a single dose and at steady state. The pharmacokinetics of two distinct age groups (> or =50, < or =65, N=15 and > or =70 years old, N=9) were compared. There were no significant differences in area under the curve (AUC) or terminal half-life between the two age groups neither after a single dose nor at steady state. However, when comparing steady state to single dose kinetics, half-life and AUC increased significantly by 42% (90% CI: 1.13, 1.78) and 28% (90% CI: 1.12, 1.47), respectively. This deviation from linearity was probably due to a partial saturation or auto-inhibition of the dominant metabolic clearance mechanism of letrozole. At steady state, approximately 70% of the administered dose was excreted in urine as unchanged letrozole (6.0+/-3.8%) or as the glucuronide of the major, pharmacologically inactive metabolite CGP44645 (64.2+/-22.7%). A single dose of letrozole caused suppression of serum estrogen levels close to the quantification limit of the assay. No difference between single dose suppression and suppression at steady state could be detected.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study

MeSH terms

  • Age Factors
  • Aged
  • Antineoplastic Agents / pharmacokinetics*
  • Area Under Curve
  • Aromatase Inhibitors*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Enzyme Inhibitors / pharmacokinetics*
  • Estrogens / blood
  • Humans
  • Letrozole
  • Middle Aged
  • Nitriles / administration & dosage
  • Nitriles / pharmacokinetics*
  • Triazoles / administration & dosage
  • Triazoles / pharmacokinetics*


  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Enzyme Inhibitors
  • Estrogens
  • Nitriles
  • Triazoles
  • Letrozole