Case Condensations OBSTETRICS Failed second-trimester misoprostol termination responding to vaginal instillation of citric acid Paul W. Whitecar, MD, Anne Zweifel, MD, and Kenneth J. Moise, Jr, MD Misoprostol, a synthetic prostaglandin analogue, has been used effectively for medical abortion in early pregnancy. 1 We present a second-trimester termination with misoprostol that appeared to be a treatment fail- ure, but in which delivery occurred rapidly after vagi- nal administration of dilute citric acid. Case A 28-year-old woman, gravida 3, para 1-0-1-1, was referred to our prenatal diagnosis unit at 22 weeks’ gestation with fetal anencephaly. After the diagnosis was confirmed by ultrasonog- raphy, the woman elected pregnancy termination. A 100-g tablet of misoprostol was placed in the posterior vaginal fornix, and treatment was repeated every 6 hours for a total of three doses. Approximately 24 hours later, the woman was reexam- ined and her cervix was unchanged. Two intact tablets were palpated in the posterior fornix. To improve absorption, we instilled 5 mL of dilute citric acid solution (Renacidin; Gynex Pharmaceuticals, Vernon Hills, IL) into the vagina. No additional doses of misoprostol were administered. Approximately 4 hours after the addition of citric acid, the woman delivered a 215-g nonviable infant without complications. At delivery, no undis- solved misoprostol tablets were found. Comment Because of its uterotonic effects, misoprostol has been used effectively in second-trimester abortion. 1 Zieman et al 2 explored the absorption kinetics of misoprostol after oral and vaginal administration. With vaginal administration, peak plasma levels were reached more slowly but were sustained longer than after oral administration. The au- thors theorized that the increased bioavailability with vaginal administration was due to avoidance of first-pass metabolism in the liver. The most common method of vaginal administration is to place the intact or fragmented tablet in the posterior fornix. Partially dissolved tablets are frequently found. Zieman et al 2 found pill fragments in seven of ten women who underwent vaginal administra- tion of misoprostol and recommended that a suppository or gel be developed. In our case, vaginal instillation of citric acid (pH 3.85) was used to simulate the acidic environment of the stomach. Orally administered misoprostol is absorbed rapidly, and peak plasma levels are achieved in less than 15 minutes. Concurrent antacid administration with oral misoprostol reduces its bioavailability. 3 Vaginal pH val- ues have never been evaluated when assessing the absorp- tion kinetics of vaginally administered misoprostol. We hypothesize that the absorption of vaginal misoprostol is a pH-dependent process. The instillation of citric acid in the vagina may improve misoprostol absorption. With misoprostol, the abortion interval varies greatly and symptoms are not typically encountered until shortly before the fetus is passed. Our case is consistent with this profile. Mishell et al 4 reported that using intravaginal misoprostol moistened with saline solution resulted in a higher success rate of early pregnancy termination. We cannot verify that the therapeutic effect was due to citric acid instillation or to moistening the tablets with this solution, but the intervention appeared beneficial in what otherwise would have been considered a treatment fail- ure. Further investigation of the vaginal absorption kinet- ics of misoprostol is needed, particularly in terms of vaginal pH and the use of acidifying agents. References 1. Jain JK, Mishell DR Jr. A comparison of intravaginal misoprostol with prostaglandin E2 for termination of second-trimester preg- nancy. N Engl J Med 1994;331:290 –3. 2. Zieman M, Fong SK, Benowitz NL, Banskter D, Darney PD. Ab- sorption kinetics of misoprostol with oral or vaginal administration. Obstet Gynecol 1997;90:88 –92. 3. Karim A, Rozek LF, Smith ME, Kowalski KG. Effects of food and antacid on oral absorption of misoprostol, a synthetic prostaglandin E1 analog. J Clin Pharmacol 1989;29:439 – 43. 4. Mishell DR Jr, Jain JK, Byrne JD, Lacarra MD. A medical method of early pregnancy termination using tamoxifen and misoprostol. Contraception 1998;58:1– 6. Received November 30, 1998. Received in revised form February 5, 1999. Accepted February 24, 1999. Copyright © 1999 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc. From the Division of Maternal-Fetal Medicine, Department of Ob- stetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 839 VOL. 94, NO. 5, PART 2, NOVEMBER 1999 0029-7844/99/$20.00 PII S0029-7844(99)00303-8