Crinone Mechanism of Action

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, Progestogens. ATC code: G03DA04.
Pharmacology: Pharmacodynamics: The properties are the same as those of naturally occurring progesterone with induction of the secretory phase in the endometrium.
Pharmacokinetics: Crinone represents a delayed-release system, based on the carbomer-polycarbophil polymer combination, which results in adhesion of the gel to the vaginal mucosa. In this way, continuous release of the active substance progesterone is achieved over a period of 72 hours maximum, and absorption is prolonged.
Relative bioavailability of Crinone is approximately 20% compared to intramuscular progesterone.
Absorption: After a single dose of Crinone, peak plasma levels of approximately 11-15 ng/ml were measured after about 7 hours.
Upon repeated once daily administration of Crinone, steady-state was achieved within the first 24 hours of treatment; mean steady-state concentrations were approximately 9 ng/ml.
Metabolism: Progesterone is mainly metabolized in the liver (by reduction, hydroxylation and conjugation) with subsequent glucuronidation of the metabolites.
The main metabolite is 3α, 5β-pregnanediol (pregnanediol).
However, it is of note that due to the vaginal application of progesterone, the hepatic first-pass effect is avoided.
Elimination: Excretion mainly takes place via the urine in the form of the pregnanediol metabolite. The elimination half-life is between 34 and 48 hours.
Special populations: There are no pharmacokinetic data available in specific patient groups (children/adolescents, elderly, hepatic and renal impairment).
Toxicology: Preclinical safety data: Due to the pronounced differences among the test animals, as well as related to humans, animal studies with progesterone possess only a limited predictive value for use in humans.
Crinone demonstrated acceptable vaginal tolerability in rabbits with higher rates of application and greater volumes than intended for therapeutic use. No evidence of a dermal sensitising potential was found in guinea-pigs using Crinone.