Misoprostol administered by epithelial routes: Drug absorption and uterine response

Abstract

Objective: To quantify and compare serum levels and uterine effects following vaginal (dry), vaginal (moistened), buccal, and rectal misoprostol administration.

Methods: Forty women seeking elective abortion between 6 and 12 6/7 weeks were randomly assigned to receive 400 mug of misoprostol by one of four routes. A 2.5-mm pressure monitoring catheter was placed through the cervix to the uterine fundus to record uterine tone and activity during the 5-hour observation period. Serum levels of misoprostol acid were measured at 15 and 30 minutes, then every 30 minutes.

Results: The four groups were similar in age, race or ethnicity, body mass index, parity, and gestation. Serum levels after vaginal, vaginal moistened and buccal administration rose gradually, peaked between 15 and 120 minutes and fell slowly. Vaginal and vaginal moistened routes produced higher peak serum levels than buccal and rectal (445.9 and 427.1 compared with 264.8 and 202.2 pg/mL; P = .03) and higher serum concentration area under the curve at 5 hours (1,025.0 and 1279.4 compared with 519.6 and 312.5 pg-hr/mL; P < .001). Uterine tone and activity, however, were similar for buccal and the two vaginal routes. After rectal administration, serum levels peaked earlier (P < .001) then dropped more abruptly, and peak uterine tone (P < .001) and total activity (P = .04) were lower than after the other routes.

Conclusion: Although serum levels were lower for buccal compared with the vaginal routes, the three routes produced similar uterine tone and activity. Rectal administration produced lower uterine tone and activity. Vaginal serum levels were two to three and a half times higher than those observed in prior misoprostol pharmacokinetic studies.