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lüll Pharmacology and pharmacokinetics of the newer generation aromatase inhibitors Buzdar AUClin Cancer Res 2003[Jan]; 9 (1 Pt 2): 468S-72SThe newer generation aromatase inhibitors (AIs) as a class show efficacy and tolerability benefits over previously established treatments in postmenopausal women with advanced breast cancer. 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) are 41-48 h, 2-4 days, and 27 h, respectively. Time to steady-state plasma levels is 7 days for both anastrozole and exemestane and 60 days for letrozole. Androgenic side effects have only been reported with exemestane. Anastrozole treatment has no impact on plasma lipid levels, whereas both letrozole and exemestane have an unfavorable effect. From indirect comparisons, anastrozole shows the highest degree of selectivity compared with letrozole and exemestane, in terms of a lack of effect on adrenosteroidogenesis. To date, there are no data suggesting any major differences in clinical efficacy between the newer generation AIs anastrozole and letrozole. Based on the observed pharmacological profiles, however, it cannot be assumed that the AIs will display the same tolerability and safety profiles when given for extended periods of time in the adjuvant setting. The effects of anastrozole, letrozole, and exemestane are being investigated in the adjuvant setting, and these data will elucidate the possible long-term consequences of the pharmacological effects reported after short-term exposure.|*Aromatase Inhibitors[MESH]|Anastrozole[MESH]|Androstadienes/pharmacokinetics/pharmacology[MESH]|Antineoplastic Agents/*pharmacokinetics/*pharmacology[MESH]|Breast Neoplasms/*drug therapy/enzymology[MESH]|Cytochrome P-450 Enzyme System/metabolism[MESH]|Drug Interactions[MESH]|Enzyme Inhibitors/*pharmacokinetics/*pharmacology[MESH]|Female[MESH]|Humans[MESH]|Letrozole[MESH]|Lipids/blood[MESH]|Nitriles/pharmacokinetics/pharmacology[MESH]|Postmenopause[MESH]|Triazoles/pharmacokinetics/pharmacology[MESH] |