Bicalutamide

Pharmacotherapeutic group:

antitumor agent, antiandrogen.
ATC code: L02BB03

Pharmacological properties:

Pharmacodynamics

Bicalutamide is an antitumor agent, is a racemic mixture with non-steroidal anti-androgenic activity, predominantly of (R) -enantiomer, does not possess any other endocrine activity. Bicalutamide binds to androgen receptors on the surface of target organ cells, suppresses the stimulating effect of androgens, without activating gene expression. The result is a regression of malignant tumors of the prostate gland. In some patients, discontinuation of bicalutamide may lead to the development of a clinical syndrome of "cancellation" of antiandrogens.

Pharmacokinetics

Suction:

After oral administration, bicalutamide is rapidly and completely absorbed from the gastrointestinal tract. Food intake does not affect the bioavailability of the drug. The time to reach the maximum concentration (TCmax) of the (R) -enantiomer is 31.3 hours.

Distribution:

Communication with plasma proteins is high (for the racemic mixture - 96%, for the (R) -enantiomer 99%).

Metabolism:

Intensively metabolized in the liver (by oxidation and the formation of conjugates with glucuronic acid) to inactive (S) - and active (R) -enantiomers.

Excretion:

Bicalutamide is excreted in the form of metabolites by the kidneys and with bile in equal proportions. (S) -enantiomer is eliminated from the body much faster (R) -enantiomer, the elimination half-life (T1 / 2) of the latter is about 7 days. With daily intake of bicalutamide, the concentration of (R) -enantiomer in plasma increases by about 10 times due to prolonged T1 / 2, which makes it possible to take the drug 1 time per day. With a daily intake of bicalutamide at a dose of 50 mg, the equilibrium concentration (Css) of the (R) -enantiomer in plasma is about 9 μg / ml. When taking 150 mg of bicalutamide daily, the equilibrium concentration of the (R) -enantiomer is approximately 22 μg / ml. At equilibrium, about 99% of all enantiomers circulating in the blood are active (R) -enantiomer. The pharmacokinetics of the (R) -enantiomer do not depend on age, condition of the kidney function, or impaired mild or moderate liver function. There is evidence that in patients with severe liver failure, the elimination of the (R) -enantiomer from plasma is slowed down.