Exemestane

Absorption

42%

Toxicity

Convulsions

Description

Exemestane was launched in US and other countries for the treatment of estrogendependent tumors and postmenopausal breast cancer. It is a novel steroidal compound structurally related to the natural substrate for the biosynthesis of estrogen, androstanedione, and can be synthesized by methylidenation of androsta-1, 4-dien- 17beta-ol-3-one in 6 position then oxidation of the alcohol function. Exemestane is an irreversible inactivator of the aromatase enzyme system, so inducing in vivo a dose-related sustained suppression of serum estrogen and minimal endocrine activity. It is the first steroidal representative of the third-generation of orally active aromatase inhibitors with a highly potent and selective mechanism of action, displaying good tolerability and safety profile. In rats with DMBA-induced mammary tumors, 10 to 100 mglkg of exemestan administered po twice-daily for 4 weeks resulted in 76 to 88% regression. In women failing anti-estrogen therapy with tamoxifen, this agent has demonstrated high activity in locally advanced or metastatic disease. In addition, it may also have potential for breast cancer prevention.

The Uses of Exemestane

Labeled Exemestane, intended for use as an internal standard for the quantification of Exemestane by GC- or LC-mass spectrometry.

Background

Exemestane is an oral steroidal aromatase inhibitor used in the adjuvant treatment of hormonally-responsive (also called hormone-receptor-positive, estrogen-responsive) breast cancer in postmenopausal women. It irreversibly binds to the active site of the enzyme resulting in permanent inhibition.

What are the applications of Application

Exemestane is a CYP19 (aromatase) inhibitor

Indications

For the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.

Pharmacokinetics

Aromatase is an enzyme that converts hormones to estrogen in the body's adrenal glands. The aromatase inhibitors (AIs) are drugs that reduce estrogen levels by blocking the action of aromatase in the adrenal glands. The selective AIs (SAIs) selectively reduce levels of estrogen without interfering with levels of other steroid hormones that are produced by the adrenal gland. Drugs in this class include anastrozole (Arimidex ?), letrozole (Femara ?) and exemestane (Aromasin ?).

Metabolism

Hepatic