ABSTRACT
Misoprostol, a prostaglandin E1 analogue, is commonly administered intravaginally for cervical ripening and induction of labor. There is uncertainty regarding the correct dose because of the need to divide the tablets, and there is difficulty in removing the product when there is an adverse event. A proprietary hydrogel polymer containing a removable controlled-release reservoir dose of misoprostol is being developed for vaginal administration (misoprostol vaginal insert) to address these drawbacks while maintaining efficacy. This study investigated the pharmacokinetic profiles of these vaginal inserts and orally administered misoprostol. Twelve nonpregnant women received 100-, 200-, and 400-microg misoprostol vaginal inserts and separately received an oral dose of 200 microg of misoprostol. Values for area under the plasma concentration versus time curve, from time 0 to the last measurable concentration, were dose proportional with 481, 1026, and 2191 pg.h/mL for the 100-, 200-, and 400-microg misoprostol vaginal inserts, respectively. Maximum plasma concentrations were 33.1, 73.4, and 144 pg/mL for the 100-, 200-, and 400-microg misoprostol vaginal inserts, compared with 609 pg/mL for the 200 microg of oral misoprostol. After administration of the insert, plasma misoprostol acid levels increased gradually with time of the maximum measured plasma concentration at 5 to 9 hours. Following removal of the insert, misoprostol acid was eliminated rapidly from the systemic circulation with a mean half-life <1 hour.
Subject(s)
Delayed-Action Preparations/pharmacokinetics , Misoprostol/pharmacokinetics , Administration, Intravaginal , Administration, Oral , Adolescent , Adult , Area Under Curve , Chromatography, High Pressure Liquid , Colic/chemically induced , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/adverse effects , Dose-Response Relationship, Drug , Drug Design , Female , Half-Life , Humans , Hydrogels , Misoprostol/administration & dosage , Misoprostol/adverse effects , Oxytocics/administration & dosage , Oxytocics/adverse effects , Oxytocics/pharmacokinetics , Polymers , Tablets , Tandem Mass Spectrometry , Time FactorsABSTRACT
OBJECTIVE: To assess the ability of a controlled-release misoprostol vaginal insert to induce labor using dose reservoirs of 25, 50, 100, and 200 microg. METHODS: This double-blind, dose ranging, randomized study was carried out in parous women requiring induction of labor at term. Each woman was randomly assigned to receive a single misoprostol vaginal insert that could remain in place for up to 24 hours and was removed for onset of active labor, an adverse event, or having reached 24 hours in situ. The primary outcome measure was time from insertion of the misoprostol vaginal insert to vaginal delivery of the neonate. RESULTS: A total of 124 women participated in the study. The median time to vaginal delivery was 27.5, 19.1, 13.1, and 10.6 hours for the 25-, 50-, 100-, and 200-microg doses, respectively. The percentage of women who delivered vaginally within 12 hours was 9%, 14%, 47%, and 53% (P<.001 using the 25-microg group as the comparator) and within 24 hours was 42%, 79%, 81%, and 70% (P=.003). Uterine hyperstimulation syndrome occurred in one woman who received the 25-mug, two women who received the 100-microg, and three women who received the 200-microg dose reservoirs. CONCLUSION: Misoprostol vaginal inserts effectively induced labor in pregnant parous women at term. LEVEL OF EVIDENCE: I.