ABSORPTION KINETICS OF MISOPROSTOL WITH ORAL OR VAGINAL ADMINISTRATION

Objective: To compare the pharmacokinetics of vaginal and oral adminis tration of the prostaglandin E-1 analogue, misoprostol. Methods: Twent y women received 400-mu g doses of misoprostol either orally or as tab lets placed in the vagina. Serum levels of the principal metabolite, m isoprostol acid, were measured at 7.5, 15, 30, 45, 60, 90, 120, and 24 0 minutes. The first ten women were pregnant and undergoing first-trim ester abortions, and the last ten were not pregnant and had additional blood sampling at 360 minutes. We compared the pharmacokinetics of mi soprostol acid after oral and vaginal administration. Results: All 20 subjects completed the study. The maximum mean (+/- standard deviation [SD]) of misoprostol acid differed significantly between the oral and vaginal groups (277 +/- 124 compared with 165 +/- 86 pg/mL, respectiv ely; P = .03, analysis of variance), as did the mean a SD time to peak levels (34 +/- 17 compared with 80 +/- 27 minutes, respectively; P < .001) and areas under the misoprostol concentration versus time curve (mean +/- SD) up to 4 hours (n = 20, 273.3 +/- 110.0 compared with 503 .3 +/- 296.7 pg.hour/mL, respectively; P = .033) and up to 6 hours (n = 10, 300.0 +/- 103.3 compared with 956.7 +/- 541.7 pg.hour/mL, respec tively; P = .029). The extent of absorption was highly variable among subjects in each group. Conclusion: There are significant differences in the pharmacokinetics of misoprostol administered by vaginal and ora l routes that may explain the difference observed in clinical efficacy . Assuming that the pharmacologic effect of misoprostol is related to its concentration in the plasma, our observation of the prolonged seru m concentrations in the vaginal group suggests that vaginal administra tion could be dosed at longer intervals than oral. (C) 1997 by The Ame rican College of Obstetricians and Gynecologists.