Dostinex (cabergoline) tablets 0.5 mg. №2

Description

Dostinex  Composition
active substance: cabergoline;

1 tablet contains 0.5 mg cabergoline;

Dostinex  excipients: leucine, lactose.

Dostinex  Dosage form
Pills.

Basic physical and chemical properties: white, flat, oblong tablets with an engraving “PU”, separated by a notch on one side and an engraving “700” and a slight notch above and below the central “0” on the other side.

Pharmacotherapeutic group
Means used in gynecology. Prolactin inhibitors. ATX code G02C B03.

Pharmacodynamics
Cabergoline is a dopaminergic ergot derivative with strong and prolonged prolactin-lowering activity. The drug directly stimulates D2-dopamine receptors on the surface of the pituitary lactotropic cells, thus inhibiting the secretion of prolactin. This substance reduces the secretion of prolactin in rats when administered orally at a dose of 3-25 μg / kg and in vitro at a concentration of 45 pg / ml. In addition, cabergoline exerts a central dopaminergic effect through the stimulation of D2 receptors at oral doses in excess of those that are effective in lowering serum prolactin levels. The long-term effect of Dostinex on the reduction of prolactin levels is probably associated with its long-term persistence in the target organ, as indicated by the slow rate of elimination of total radioactivity from the pituitary gland after a single oral dose in rats (t½ is approximately 60 hours).

Pharmacodynamic effects were studied in healthy volunteers, postpartum women, and patients with prolactinemia. After a single dose of the drug in a dose of 0.3-1.5 mg, a significant decrease in plasma prolactin levels is observed in each of the studied populations. This effect develops quickly – within 3 hours after drug administration and persists for 7-28 days in healthy individuals and patients with hyperprolactinemia and for 14-21 days in women after childbirth.

The degree of reduction in prolactin levels and the duration depend on the dose.
For the endocrine effects of Dostinex, which are not associated with antiprolactinemic action, the available data from studies involving humans confirm the experimental results obtained in animal studies and show that the test substance is characterized by a high selective effect and does not affect the basal level of secretion of other pituitary hormones and cortisol. … The pharmacodynamic effect of the drug Dostinex did not correlate with the therapeutic effect of blood pressure lowering alone. The maximum hypotensive effect of the drug in a single dose is usually observed within the first 6 hours after administration and depends on the dose for both maximum reduction and frequency.

Pharmacokinetics
The pharmacokinetics and metabolic profiles of Dostinex were studied in healthy volunteers of both sexes and in female patients with hyperprolactinemia.

After ingestion of a substance labeled with a radioactive label, it was rapidly absorbed from the gastrointestinal tract, and the peak of radioactivity in plasma was reached in 0.5-4 hours.

10 days after application of the drug, about 18% and 72% of the radioactive dose was excreted in the urine and feces, respectively. The content of unchanged drug in urine was 2-3% of the administered dose.

The main metabolite identified in urine was 6-allyl-8b-carboxy-ergoline, which accounted for 4-6% of the drug dose. Three additional metabolites were found in urine, which in total accounted for less than 3% of the drug dose. The activity of metabolites in vitro with respect to suppressing the secretion of prolactin is significantly less than that of cabergoline. The metabolism of cabergoline was also studied in the blood plasma of healthy male volunteers treated with [14C] -cabergoline: it was found that cabergoline is subject to rapid and significant biotransformation.

The low level of urinary excretion in unchanged cabergoline has also been confirmed in studies using a non-radioactive drug. The half-life of cabergoline, which was determined by the rate of excretion of the drug in the urine, is long: 63-68 hours in healthy volunteers (using radioimmunoassay) and 79-115 hours in patients with hyperprolactinemia (using the HPLC method).

Taking into account the half-life, the equilibrium state should be achieved after 4 weeks, which was confirmed by the average values ​​of the maximum concentration of cabergoline in blood plasma after a single use (37 ± 8 pg / ml) and after 4 weeks with repeated use (101 ± 43 pg / ml ).

The results of in vitro experiments showed that the drug in concentrations of 0.1-10 ng / ml 41-42% binds to blood plasma proteins. Food does not affect the absorption and distribution of the drug.