Pharmacokinetic Profiles of Controlled‐Release Hydrogel Polymer Vaginal Inserts Containing Misoprostol

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.