Pharmacokinetics and adverse-effect profile of rectally administered misoprostol in the third stage of labor

Abstract Objective To characterize the pharmacokinetics and adverse-effect profile of rectally administered misoprostol. Methods To assess absorption of rectally administered misoprostol, 20 women were randomized to receive misoprostol 600 μg by either oral or rectal administration after delivery. Blood samples were obtained at 0, 7.5, 15, 30, 45, 60, 90, 120, and 240 minutes and analyzed for serum concentrations of misoprostol free acid by enzyme-linked immunosorbent assay. Additionally, 275 women were randomized to receive rectal 400 μg, rectal 600 μg, or oral 600 μg misoprostol after delivery. Self-assessment questionnaires were used to ascertain the adverse-effect profiles. Results Misoprostol tablets are absorbed rectally even though they are formulated for oral use. The area under the curve (integral of concentration and time graph) for rectal misoprostol was higher by 121 pg.h/mL (95% confidence interval [CI] −4.2, 246.2) than for oral misoprostol. The rectal route group had a mean maximum serum concentration 144 pg/mL lower than that for the oral route (95% CI 63, 225). This maximum was achieved on average 23 minutes later than in the oral group (95% CI 10, 35). Shivering was reported by 76% of the patients in the oral 600-μg arm, 56% of the patients in the rectal 400-μg arm, and 54% of the patients in the rectal 600-μg arm. The relative risk of shivering in the combined rectal groups is 73% that of the oral group (95% CI 61%, 86%). Severe shivering reported by patients was significantly reduced, by 72%, in rectal groups compared with the oral group (95% CI 60%, 81%). Conclusion Misoprostol administered rectally is associated with lower peak levels and a reduction in adverse effects compared with the oral route. Increasing rectal doses may achieve higher efficacy without reducing the acceptability of the treatment.