Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Sex hormones and modulators of the genital system; Progestogens; Pregnen-(4) derivatives, ATC code: G03DA04.
Progesterone is a naturally occurring steroid that is secreted by the ovary, placenta, and adrenal glands. In the presence of adequate estrogen,
progesterone transforms a proliferative endometrium into a secretory endometrium. Progesterone is necessary to increase endometrial receptivity for implantation of an embryo. Once an embryo is implanted, progesterone acts to maintain the pregnancy.

Clinical efficacy and safety
Ongoing pregnancy rates following 10-week luteal support with Prolutex 25 mg/day (N= 318) in patients who had an embryo transfer in the Phase III clinical trial were 29.25% (95% CI: 24.25 - 34.25).

Paediatric population
The European Medicine Agency has waived the obligation to submit the results of studies with Prolutex in all subsets of the paediatric population in the granted indications

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Absorption
Progesterone serum concentrations increased following the subcutaneous (s.c.) administration of 25 mg of Prolutex to 12 healthy post-menopausal females.
By one hour post-administration of a single s.c. dose the mean Cmax was 50.7±16.3 ng/ml. The progesterone serum concentration decreased following a mono-exponential decay, and by twelve hours post-administration the average concentration was 6.6±1.6 ng/ml. The minimum serum concentration, 1.4±0.5 ng/ml, was reached at the 96-hour time-point. Pharmacokinetic analysis demonstrated linearity of the three s.c. doses tested (25 mg, 50 mg and 100 mg).
Following multiple dosing of 25 mg/daily via subcutaneous administration, steady state concentrations were attained within approximately 2 days of treatment with Prolutex. Trough values of 4.8 ± 1.1 ng/mL were observed with AUCs of 346.9 ± 41.9 ng*hr/mL on Day 11.

Distribution
In humans, 96-99% of progesterone is bound to serum proteins like albumin (50-54%) or transcortin (43-48%), and the remainder is free in the plasma.
Owing to its lipid solubility, progesterone travels from the bloodstream to its target cells through passive diffusion.

Biotransformation
Progesterone is metabolized primarily by the liver largely to pregnanediols and pregnanolones. Pregnanediols and pregnanolones are conjugated in the liver to glucuronide and sulfate metabolites. Progesterone metabolites that are excreted in the bile may be deconjugated and may be further metabolized in the gut via reduction, dehydroxylation, and epimerization.

Excretion
Progesterone undergoes renal and biliary elimination.