Pharmacodynamics<unk>  is an oral steroidal aromatase inhibitor that is used in ER-positive breast cancer in addition to surgery and/or radiation in post-menopausal women. The main source of estrogen is the ovaries in premenopausal women, while in post-menopausal women most of the body's estrogen is produced via the conversion of androgens into estrogen by the aromatase enzyme in the peripheral tissues (i.e. adipose tissue like that of the breast) and a number of sites in the brain. Estrogen is produced locally via the actions of the aromatase enzyme in these peripheral tissues where it acts locally. Any circulating estrogen in post-menopausal women as well as men is the result of estrogen escaping local metabolism and entering the circulatory system.<unk>  is an irreversible, steroidal aromatase inactivator of type I, structurally related to the natural substrate 4-androstenedione. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect also known as "suicide inhibition." By being structurally similar to enzyme targets,<unk>  permanently binds to the enzymes, preventing them from converting androgen into estrogen. Type II aromatase inhibitors such as anastrozole and letrozole, by contrast, are not steroids and work by interfering with the aromatase's heme. A study conducted on young adult males found that the estrogen suppression rate for<unk>  varied from 35% for estradiol (E2) to 70% for estrone (E1). Pharmacokinetics<unk>  is quickly absorbed from the gut, but undergoes a strong first-pass effect in the liver. Highest blood plasma concentrations are reached after 1.2 hours in breast cancer patients and after 2.9 hours in healthy subjects. Maximal aromatase inhibition occurs after two to three days. 90% of the absorbed substance are bound to plasma proteins. The liver enzyme CYP3A4 oxidizes the methylidene group in position 6, and the 17-keto group (on the five-membered ring) is reduced by aldo-keto reductases to an alcohol. Of the resulting metabolites, 40% are excreted via the urine and 40% via the feces within a week. The original substance accounts for only 1% of excretion in the urine. The terminal half-life is 24 hours.
Exemestane
Anastrozole
Salvestrol
Hexestrol
Fosfestrol
Norendoxifen
Tamoxifen
Formestane