Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: Progestogens. ATC Code: L02A B

Medroxyprogesterone acetate has the pharmacological action of a progestogen.
MPA is a synthetic progestin (structurally related to the endogenous hormone progesterone), which has been demonstrated to possess several pharmacological actions on the endocrine system:
•        Inhibition of pituitary gonadotropins (FSH and LH);
•        Decrease of ACTH and hydrocortisone blood levels;
•        Decrease of circulating testosterone;
•        Decrease of circulating estrogen levels (as the result of both FSH inhibition and enzymatic induction of hepatic reductase, resulting in increased clearance of testosterone and consequent decreased conversion of androgens to estrogens).
All of these actions result in a number of pharmacological effects, as described below.


Oncology
MPA demonstrates antitumor activity. When MPA is given to patients at high doses (either by the oral route or by intramuscular injection) it is effective in the palliative treatment of hormone-responsive, malignant neoplasms.

Pharmacokinetic Properties

5.2    Pharmacokinetic properties

Absorption: Oral MPA is rapidly absorbed with maximum concentration obtained between 2 to 4 hours. The half-life of oral MPA is approximately 17 hours. It is 90% protein bound, and is mainly excreted in the urine.
Administration with food increases the bioavailability of MPA. A 10 mg dose of oral MPA, taken immediately before or after a meal, increased average MPA Cmax (51% and 77%, respectively) and average AUC (18% and 33%, respectively). The half-life of MPA was not changed with food.
Distribution: MPA is approximately 90% protein bound, primarily to albumin; no MPA binding occurs with sex-hormone binding globulin. The unbound MPA modulates pharmacologic responses.
Metabolism: Following oral dosing, MPA is extensively metabolized in the liver via ring A and/or side-chain hydroxylation, with subsequent conjugation and elimination in the urine.
At least 16 MPA metabolites have been identified. In a study designed to measure the metabolism of MPA, the results suggest that human cytochrome P450 3A4 is primarily involved in the overall metabolism of MPA in human liver microsomes.
Elimination: Most MPA metabolites are excreted in the urine as glucuronide conjugates with only minor amounts excreted as sulfates. Mean percent dose excreted in the 24-hour urine of patients with fatty liver as intact MPA after a 10 mg or 100 mg dose was 7.3% and 6.4%, respectively. Elimination half-life of oral MPA is 12 to 17 hours.