Pharmacokinetic Analysis of Hourly Oral Misoprostol Administration – A Pilot Study

Abstract

Objective: To conduct a pilot study of optimal misoprostol dosing to induce moderate labor among woman and to understand the pharmacokinetic parameters of moderate labor induction or augmentation. Methods:We administered high doses of oral misoprostol (200 μg) hourly to nine mid-trimester pregnant women who had requested termination of gestation to determine whether misoprostol metabolites (misoprostol acid, MPA) accumulated in the blood plasma. We then chose five pregnant women at term to receive individual hourly oral misoprostol administration program and measured plasma concentrations of MPA at various stages of labor including the beginning of misoprostol solution administration, the initial response of regular uterine contractions, and full cervical dilation. Results:The concentration of MPA, which is responsible for misoprostol's clinical activity and toxicity, had no obvious accumulation after high-dose hourly oral misoprostol administration. Furthermore, the five moderate dosing programs of hourly oral misoprostol administration ripened the cervix with very low concentrations of MPA detected in the plasma. Conclusions:The preliminary results show that the five defined programs in labor induction or augmentation are promising dosing regimens that avoid uterine hyperstimulation, shorten the labor course, and prevent the risk of potential toxicity from excess MPA.