Dinoprostone

Dinoprostone is a prostaglandin of the E series with actions on smooth muscle; the endogenous substance is termed prostaglandin E₂. It induces contraction of uterine muscle at any stage of pregnancy and is reported to act predominantly as a vasodilator on blood vessels and as a bronchodilator on bronchial muscle.

It is postulated that vaginal absorption of PGE₂ stimulates endogenous PGE₂ and PGF_2α production, similar to that which is seen in spontaneous labour.

Vaginal administration

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. PGE₂ is rapidly metabolised to 13, 14-dihydro, 15-keto PGE₂ which is converted to 13, 14-dihydro, 15-keto PGA₂ which binds covalently to albumen.

There has been found to be inter-patient variability regarding systemic absorption of PGE₂. This can be attributed to different conditions of the vaginal mucosa between patients.

IV administration

Dinoprostone is rapidly metabolised in the body. Intravenous administration results in very rapid distribution and metabolism, with only 3% of unchanged drug remaining in the blood after 15 minutes. At least nine PGE2 metabolites have been identified in human blood and urine.

Animal studies lasting several weeks at high doses have shown that prostaglandins of the E and F series can induce proliferation of bone. Such effects have also been noted in newborn infants who received prostaglandin E₁ during prolonged treatment. There is no evidence that short-term administration of prostaglandin E₂ can cause similar bone effects.