Comparison between oral and vaginal administration of misoprostol on uterine contractility

Objective: To compare the degree of absorption and the effect on uterine contractility of the prostaglandin E₁ analogue misoprostol after vaginal and oral administration. Methods: Thirty women with a normal intrauterine pregnancy between 8 and 11 weeks' gestation who requested termination of pregnancy were given either 0.2 mg (orally n = 5; vaginally n = 6) or 0.4 mg (orally n = 10; vaginally n = 9) of misoprostol. Intrauterine pressure was recorded using a Grass polygraph connected to a pressure transducer 30 minutes before misoprostol was given and for 4 hours thereafter. At the end of the recording, suction curettage was performed. Blood samples were obtained at 0, 0.5, 1, 2, 4, and 6 hours for measurement of misoprostol, which was assayed by high-pressure liquid chromatography-mass spectrometry. Results: In all patients, the first effect was an increase in uterine tonus. After 0.4 mg of misoprostol administered orally, uterine tonus started to increase after a mean (± standard deviation) time of 7.8 ± 3.0 minutes and reached its maximum after 25.5 ± 5.0 minutes. The corresponding times after vaginal administration were 20.9 ± 5.3 minutes and 46.3 ± 20.7 minutes, respectively. The initial increase in tonus was also more pronounced after oral than after vaginal administration. After vaginal administration, all patients developed uterine contractions; the activity, measured in Montevideo units, increased continuously during the observation period. This was not the case after oral administration. Plasma levels of misoprostol were measured in 18 patients. The highest levels were found 30 minutes after oral treatment and 1-2 hours after vaginal administration. Conclusion: The long-lasting and continuously increasing uterine contractility after vaginal administration can be explained only in part by a direct effect of misoprostol. The longer period of elevated plasma levels of misoprostol may also have initiated the prolonged events leading to increased uterine contractility.