An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane

Cancer. 2002 Nov 1;95(9):2006-16. doi: 10.1002/cncr.10908.


Background: The newer generation, nonsteroidal aromatase inhibitors (AIs) anastrozole and letrozole have shown superior efficacy compared with tamoxifen as first-line treatments and compared with megestrol acetate as second-line therapy in postmenopausal women with advanced breast carcinoma. In an open-label, Phase II trial, it was reported that exemestane showed numerical superiority compared with tamoxifen for objective response and clinical benefit. Because these agents ultimately may be administered for periods of up to 5 years in the adjuvant setting, it is of increasing importance to assess their tolerability and pharmacologic profiles.

Methods: In the absence of data from direct clinical comparisons, the published literature was reviewed for the clinical pharmacology, pharmacokinetic characteristics, and selectivity profiles of anastrozole, letrozole, and exemestane.

Results: At clinically administered doses, the plasma half-lives of anastrozole (1 mg once daily), letrozole (2.5 mg once daily), and exemestane (25 mg once daily) were 41-48 hours, 2-4 days, and 27 hours, respectively. The time to steady-state plasma levels was 7 days for both anastrozole and exemestane and 60 days for letrozole. Androgenic side effects have been reported only with exemestane. Anastrozole treatment had no impact on plasma lipid levels, whereas both letrozole and exemestane had an unfavorable effect on plasma lipid levels. In indirect comparisons, anastrozole showed the highest degree of selectivity compared with letrozole and exemestane in terms of a lack of effect on adrenosteroidogenesis.

Conclusions: All three AIs demonstrated clinical efficacy over preexisting treatments. However, there were differences in terms of pharmacokinetics and effects on lipid levels and adrenosteroidogenesis. The long-term clinical significance of these differences remains to be elucidated.

Publication types

  • Review

MeSH terms

  • Anastrozole
  • Androstadienes / adverse effects
  • Androstadienes / pharmacokinetics*
  • Androstadienes / pharmacology
  • Androstadienes / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Aromatase Inhibitors*
  • Breast Neoplasms / drug therapy
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacokinetics*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Humans
  • Letrozole
  • Nitriles / adverse effects
  • Nitriles / pharmacokinetics*
  • Nitriles / pharmacology
  • Nitriles / therapeutic use
  • Triazoles / adverse effects
  • Triazoles / pharmacokinetics*
  • Triazoles / pharmacology
  • Triazoles / therapeutic use


  • Androstadienes
  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Enzyme Inhibitors
  • Nitriles
  • Triazoles
  • Anastrozole
  • Letrozole
  • exemestane