Aromasin® [Exemestane]

Aromasin® - inhibiting the synthesis of estrogen, antitumor.

Blocks aromatase and stops the synthesis of estrogen (without affecting the production of other steroid hormones, such as cortisol and aldosterone).

Irreversible steroid aromatase inhibitor, similar in structure to the natural substance androstenedione. In postmenopausal women, estrogens are produced predominantly by the conversion of androgens into estrogens by the action of the aromatase enzyme in peripheral tissues. Blocking the formation of estrogen by inhibiting aromatase is an effective and selective treatment for hormone-dependent breast cancer in postmenopausal women. The mechanism of action of the drug Aromazin® is due to the fact that it irreversibly binds to the active fragment of the enzyme, causing its inactivation.

In postmenopausal women, Aromazin® reliably decreases the serum estrogen concentration starting at a dose of 5 mg, and the maximum reduction (> 90%) is achieved with doses of 10-25 mg. In postmenopausal patients with a diagnosis of breast cancer who received 25 mg of the drug daily, the overall level of the enzyme aromatase in the body decreased by 98%.

Exemestane does not possess progestogenic and estrogenic activity. Only insignificant androgenic activity is detected, mainly when used in high doses.

Aromasin® does not affect the biosynthesis of cortisol and aldosterone in the adrenal glands, which confirms the selectivity of the drug. In this regard, there is no need for replacement therapy with glucocorticoids and mineralocorticoids.

With the use of the drug, even in low doses, there is a slight increase in the content of LH and FSH in the serum, which is characteristic of drugs of this pharmacological group and probably develops on the basis of feedback at the pituitary level: a decrease in the concentration of estrogen stimulates the secretion of gonadotropins in the pituitary gland also postmenopausal women.

Pharmacokinetics

Suction

After oral administration, exemestane is rapidly absorbed, mainly from the digestive tract. The absolute bioavailability of the drug has not been established. It is assumed that it is limited by the extensive effect of the first passage through the liver. With a single dose of the drug in a dose of 25 mg C_max in plasma it is 17 ng / ml and is reached in 2 hours. Simultaneous food intake increases the bioavailability of the drug by 40%.

The pharmacokinetic parameters of exemestane are linear.

Distribution

Communication with plasma proteins is approximately 90%. Exemestane and its metabolites do not bind to red blood cells. With repeated use of unpredictable cumulation of exemestane is not observed.

Metabolism

The process of biotransformation of exemestane is carried out by oxidation of the methylene group at 6 position under the action of the isoenzyme CYP3A4 and / or reduction of the 17-keto group under the action of aldoketoreductase with subsequent conjugation. The metabolites of exemestane are either inactive or less active in relation to the inhibition of aromatase than the parent compound.

Removal

Final t_1/2 approximately 24 hours. Approximately equal amounts of exemestane (about 40%) are excreted in the urine and feces during the week. From 0.1 to 1% is excreted in the urine unchanged.

Pharmacokinetics in special clinical situations

A pronounced relationship between systemic exposure of the drug and age has not been established.

In patients with severe renal failure (CC <30 ml="" min="" systemic="" exposure="" to="" exemestane="" is="" 2="" times="" higher="" but="" dose="" adjustment="" not="" required="" p="">

In patients with moderate or severe hepatic impairment systemic exposure to exemestane is 2–3 times higher, but dose adjustment is not required.