General information about Exemestane in the UK
Steroid-generation aromatase inhibitor III, similar in structure to androstenedione. Crystalline powder from white to white with a yellowish tinge. It is soluble in N, N-dimethylformamide, soluble in methanol, practically insoluble in water. Molecular Weight - 296.41.
Mode of action - anti-tumor, anti-estrogen.
In the UK it inhibits aromatase (irreversibly binds to the active site of the enzyme and causing its inactivation) and blocks the formation of estrogens. Has anti-estrogenic effects, does not possess progestogenic and estrogenic activity does not affect the synthesis of cortisol and aldosterone in the adrenal glands. In high doses, it shows little androgenic activity (due to the 17-gidroproizvodnym). It increases the level of LH and FSH on the feedback principle: reducing the concentration of estrogen stimulates the secretion of gonadotropins in the pituitary gland.
It is dose-dependent decrease in estrone, estradiol, and estrone sulfate. Reduction of estrogen concentrations in the serum of postmenopausal women is shown at a dose of 5 mg and reaches a maximum (reduction by more than 90%) at a dose of 10-25 mg (maximum reduction in estrogen levels is observed for 3 days). In postmenopausal women with breast cancer when taking exemestane 25 mg / day reduced the overall level of aromatase by 98%.
In a multicenter, randomized, double-blind phase III trial Clinical trials have shown high efficacy and safety of exemestane in the treatment of post-menopausal women suffering from progressive metastatic breast cancer whose prior tamoxifen therapy was ineffective.
After intake of rapidly absorbed (food improves absorption achieved with a 40% higher plasma levels than in the fasting state). With a single application of 25 mg Cmax after administration of food (18 ng / ml) is achieved within 2 hours. Plasma protein binding is 90% and is independent of the total concentration. It is well distributed in the tissues. It is metabolized by oxidation of the methylene group in position 6 involving CYP3A4 isoenzyme and / or by reducing the 17-keto involving aldoketoreduktaz to form inactive or less active metabolites. T1 / 2 - 24 hours. Return with urine (less than 1% in unchanged form) and faeces in equal parts within 1 week.
Application of the substance Exemestane
breast cancer in postmenopausal women (natural or induced), progressing against the background of antiestrogen therapy, non-steroidal aromatase inhibitors or progestins.