Prospects for the use of prostaglandin 11-deoxymisoprostol in obstetrics and gynecology: For medical abortion and the induction and initiation of labor (experimental work)

Abstract

BACKGROUND: According to WHO (2015), abortion complications account for 8% of maternal deaths. These statistics have prompted the search for new ways to safely terminate early pregnancy. In 2010, at the World Congress of Obstetricians and Gynecologists in Lisbon, medical abortion was called a “world revolution.” Due to the introduction of medical abortion, maternal mortality after abortion decreased by 20,000 persons in 2012. Medical abortion using prostaglandin preparations, which can be used to solve this problem, is safer than surgical abortion, since curettage of the uterine cavity can cause inflammation, mechanical trauma, and infertility. In the Russian Federation, a prostaglandin preparation (misoprostol 200 mcg) has been certified for medical termination of pregnancy. However, this drug is expensive, as it is manufactured through complex chemical synthesis. At the Ufa Institute of Chemistry, Russian Academy of Sciences (UIC, RAS), due to a directed search for uterotonics among 11-deoxyprostaglandins of the E- and F-groups, a promising analog of prostaglandin E1 with a higher uterotonic activity than misoprostol was revealed. The agent is 11-deoxymisoprostol (11-DMP), which is several times cheaper and more accessible for synthesis.

AIM: This study aimed to compare the pharmacological properties of misoprostol and 11-deoxymisoprostol.

MATERIALS AND METHODS: The experiments were performed on non-linear white rats weighing 190–210 g. The animals were fed with a standard diet for the entire experimental period. Animals were monitored and assessed on a daily basis. Animals were divided into six experimental groups, using their body weight as the main criterion for randomization (deviation of body weight values within the group was no more than 10%), with 20 animals in each experimental group. The drug was administered intragastrically at a dose of 10 mg/kg.

To assess the immunotoxic properties, we studied the indicators of nonspecific and specific humoral immunity and cellular immunity in rats and assessed its effect on the mass of lymphoid organs and their cellularity. The allergenic properties of 11-DMP were evaluated using the methods of anaphylactic shock, indirect reaction of mast cell degranulation, reaction of immune complexes, and conjunctival test.

RESULTS: After administration of 11-DMP, a decrease in the rate of weight gain, changes in behavior, and death of animals were not observed in any of the studied groups of males or females. The fertility index did not differ significantly in all experimental groups.

The average number of fetuses per female, the sex ratio of rat pups, and the death rate of newborn rat pups did not change in the broods of all experimental groups.

The study of the allergenic effect of the drug revealed that 11-DMP does not have allergenic properties, as shown by the reactions of mast cell degranulation, immune complexes, and the conjunctival test.

CONCLUSIONS: When studying the pharmacological properties, it was revealed that 11-DMP compared with misoprostol has higher uterotonic properties; the therapeutic margin is 2 times greater, the toxicity is 2 times lower, and it is more stable and has a more accessible route of chemical synthesis.

Keywords

prostaglandins / misoprostol / medical abortion / stimulation of labor activity / 11-deoxymisoprostol (11-DMP) / uterotonic activity

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