Prostin E2 Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action/Effect: For uterine stimulation: Dinoprostone stimulates the myometrium of the gravid uterus to contract in a manner that is similar to the contractions seen in the term uterus during labor. Whether or not this action results from a direct effect of dinoprostone on the myometrium has not been determined. Nonetheless, the myometrial contractions induced by the vaginal administration of dinoprostone are sufficient to produce evacuation of the products of conception from the uterus in the majority of cases.
For cervical ripening: Dinoprostone has a local cervical effect in initiating softening, effacement, and dilation. These changes, referred to as cervical ripening, occur spontaneously as the normal pregnancy progresses toward term and allow evacuation of uterine contents by decreasing cervical resistance at the same time that myometrial activity increases.
Other actions: Dinoprostone is also capable of stimulating smooth muscle of the gastrointestinal tract in humans. This activity may be responsible for the vomiting and/or diarrhea that is occasionally seen when dinoprostone is used for preinduction cervical ripening.
In laboratory animals, and also in humans, large doses of dinoprostone can lower blood pressure, probably as a result of its effect on smooth muscle of the vascular system. Dinoprostone can also elevate body temperature; however, with the dose of dinoprostone used for cervical ripening, these effects have not been seen.
Pharmacokinetics: General characteristics of active substances: Absorption: When administered vaginally, dinoprostone is rapidly absorbed. Dinoprostone is 73% bound to human plasma albumin.
Following insertion of the vaginal tablet, PGE₂ absorption (as measured by the presence of PGE₂ metabolites) increases to reach a peak at about 40 minutes.
Distribution and Metabolism: Dinoprostone is widely distributed in the mother.
PGE₂ is rapidly metabolized to 13, 14-dihydro-15-keto PGE₂, which is converted to 13, 14-dihydro, 15-keto PGA2. Dinoprostone is completely metabolized in humans. It is extensively metabolized in the lungs, and the resulting metabolites are further metabolized in the liver and kidney.
Elimination: The drug and its metabolites are excreted primarily by the kidneys, with a small amount excreted in the feces.
Toxicology: Preclinical safety data: Carcinogenesis, mutagenesis, impairment of fertility: Carcinogenic bioassay studies have not been conducted in animals with dinoprostone due to the limited indications for use and short duration of administration. No evidence of mutagenicity was observed in the Micronucleus Test or Ames Assay.