AROMASIN – exemestane 25mg/100tabs

Description

AROMASIN is an irreversible steroidal aromatase inhibitor, similar in structure to the natural substance androstenedione. In postmenopausal women, estrogens are produced predominantly by the conversion of androgens to estrogens by the action of the aromatase enzyme in peripheral tissues. Blocking estrogen production by inhibiting aromatase is an effective and selective treatment for hormone-dependent breast cancer in postmenopausal women. In postmenopausal women, exemestane significantly reduces the concentration of estrogen in the blood serum, starting with a dose of 5 mg, the maximum decrease (> 90%) is achieved with a dose of 10-25 mg. In postmenopausal patients diagnosed with breast cancer who received 25 mg daily, total aromatase levels were reduced by 98%.

Exemestane has no progestogenic and estrogenic activity. A small androgenic activity, probably associated with 17-hydroderivative, was observed mainly with the use of the drug in high doses. In studies of long-term daily use, exemestane did not affect the biosynthesis of hormones such as cortisol or aldosterone, the levels of which changed before or after the ACTH test; this demonstrated selectivity for other enzymes involved in hormonal metabolism. In this regard, there is no need for replacement therapy with corticosteroids and mineralocorticoids.

A slight increase in the level of LH and FSH in the blood serum is observed even at low doses; however, this effect is expected for drugs of this pharmacological group; probably, it develops according to the feedback principle, at the level of the pituitary gland: a decrease in the concentration of estrogens stimulates the secretion of gonadotropins by the pituitary gland (also in postmenopausal women).

Pharmacokinetics.

Absorption. After administration, exemestane is rapidly absorbed. The dose is absorbed from the gastrointestinal tract, high. Absolute bioavailability has not been established, although distribution should be limited by the first pass effect. With a single dose of 25 mg, the average plasma level reaches a maximum after 2:00 and is 18 ng / ml. Simultaneous use of the drug with food increases its bioavailability by 40%.

Distribution. The volume of distribution of exemestane without correction for oral bioavailability is 20,000 liters. The pharmacokinetics of exemestane is linear and the terminal half-life is 24 hours. Plasma protein binding is 90% and does not depend on concentration. Exemestane and its metabolites bind to red blood cells. Exemestane does not accumulate in a nonpermissible way after repeated doses.

Metabolism and excretion. AROMASIN is metabolized by oxidation of the methylene group (6) with the help of the CYP3A4 isoenzyme and / or by reduction of the 17-keto group with aldoketoreductases, followed by conjugation. The clearance of exemestane is approximately 500 L/h without adjustment for oral bioavailability.

By inhibition of aromatase, these metabolites are either inactive or less active than the parent compound. The amount of the drug in unchanged form, excreted in the urine, is 1% of the dose. The same amount (40%) of 14C-labeled exemestane was excreted in urine and feces over a week.