Anzol Mechanism of Action

Pharmacotherapeutic group: Enzyme inhibitors. ATC code: L02B G03.
Pharmacology: Pharmacodynamics: Mechanism of action and pharmacodynamic effects: Anastrozole is a potent and highly selective non-steroidal aromatase inhibitor. In postmenopausal women, estradiol is produced primarily from the conversion of androstenedione to estrone through the aromatase enzyme complex in peripheral tissues. Estrone is subsequently converted to estradiol. Reducing circulating estradiol levels has been shown to produce a beneficial effect in women with breast cancer. In postmenopausal women, Anastrozole at a daily dose of 1 mg produced estradiol suppression of greater than 80% using a highly sensitive assay.
Anastrozole does not possess any progestogenic, androgenic, or estrogenic activity.
Daily doses of Anastrozole up to 10 mg do not have any effect on cortisol or aldosterone secretion, measured before or after standard adrenocorticotrophic hormone (ACTH) challenge testing. Corticoid supplements are therefore not needed.
Pharmacokinetics: Absorption: Absorption of anastrozole is rapid and maximum plasma concentrations typically occur within two hours of dosing (under fasted conditions). Food slightly decreases the rate but not the extent of absorption. The small change in the rate of absorption is not expected to result in a clinically significant effect on steady-state plasma concentrations during once daily dosing of Anastrozole tablets. Approximately 90 to 95% of plasma anastrozole steady-state concentrations are attained after 7 daily doses, and accumulation is 3- to 4-fold. There is no evidence of time or dose-dependency of anastrozole pharmacokinetic parameters.
Anastrozole pharmacokinetics are independent of age in postmenopausal women.
Distribution: Anastrozole is only 40% bound to plasma proteins.
Elimination: Anastrozole is eliminated slowly with a plasma elimination half-life of 40 to 50 hours. Anastrozole is extensively metabolised by postmenopausal women with less than 10% of the dose excreted in the urine unchanged within 72 hours of dosing. Metabolism of anastrozole occurs by N-dealkylation, hydroxylation and glucuronidation. The metabolites are excreted primarily via the urine. Triazole, the major metabolite in plasma, does not inhibit aromatase.
Renal or hepatic impairment: The apparent clearance (CL/F) of anastrozole, following oral administration, was approximately 30% lower in volunteers with stable hepatic cirrhosis than in matched controls (Study 1033IL/0014). However, plasma anastrozole concentrations in the volunteers with hepatic cirrhosis were within the range of concentrations seen in normal subjects in other trials. Plasma anastrozole concentrations observed during long-term efficacy trials in patients with hepatic impairment were within the range of plasma anastrozole concentrations seen in patients without hepatic impairment.
The apparent clearance (CL/F) of anastrozole, following oral administration, was not altered in volunteers with severe renal impairment (GFR <30ml/min) in Study 1033IL/0018, consistent with the fact that anastrozole is eliminated primarily by metabolism. Plasma anastrozole concentrations observed during long- term efficacy trials in patients with renal impairment were within the range of plasma anastrozole concentrations seen in patients without renal impairment. In patients with severe renal impairment, administration of Anastrozole should be performed with caution (see Dosage & Administration and Precautions).
Paediatric population: In boys with pubertal gynaecomastia (10-17 years), anastrozole was rapidly absorbed, was widely distributed, and was eliminated slowly with a half-life of approximately 2 days. Clearance of anastrozole was lower in girls (3-10 years) than in the older boys and exposure higher. Anastrozole in girls was widely distributed and slowly eliminated.