indication

For adjuvant treatment of hormone receptor positive breast cancer , as well as hormonal treatment of advanced breast cancer in post-menopausal women. Has also been used to treat pubertal gynecomastia and McCune-Albright syndrome; however, manufacturer states that efficacy for these indications have not been established.

pharmacology

Anastrozole is a potent and selective non-steroidal aromatase inhibitor indicated for the treatment of advanced breast cancer in post-menopausal women with disease progression following tamoxifen therapy. Many breast cancers have estrogen receptors and growth of these tumors can be stimulated by estrogens. In post-menopausal women, the principal source of circulating estrogen (primarily estradiol) is conversion of adrenally-generated androstenedione to estrone by aromatase in peripheral tissues, such as adipose tissue, with further conversion of estrone to estradiol. Many breast cancers also contain aromatase; the importance of tumor-generated estrogens is uncertain. Treatment of breast cancer has included efforts to decrease estrogen levels by ovariectomy premenopausally and by use of anti-estrogens and progestational agents both pre- and post-menopausally, and these interventions lead to decreased tumor mass or delayed progression of tumor growth in some women. Anastrozole is a potent and selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone.

mechanism of action

Anastrozole selectively inhibits aromatase. The principal source of circulating estrogen (primarily estradiol) is conversion of adrenally-generated androstenedione to estrone by aromatase in peripheral tissues. Therefore, aromatase inhibition leads to a decrease in serum and tumor concentration of estrogen, leading to a decreased tumor mass or delayed progression of tumor growth in some women. Anastrozole has no detectable effect on synthesis of adrenal corticosteroids, aldosterone, and thyroid hormone.

toxicity

In rats, lethality is greater than 100 mg/kg.

biotransformation

Hepatic. Metabolized mainly by N-dealkylation, hydroxylation, and glucuronidation to inactive metabolites. Primary metabolite is an inactive triazole.

absorption

Rapidly absorbed into the systemic cirulation following oral administration. Peak plasma concentrations are usually attained within 2 hours under fasting conditions, with steady-state plasma concentrations attained in approximately 7 days.

half life

50 hours

route of elimination

Hepatic metabolism accounts for approximately 85% of anastrozole elimination. Renal elimination accounts for approximately 10% of total clearance.