Pharmacokinetics of oral misoprostol for induction of labor in pregnancies complicated by obesity

Abstract

Birthing parents with obesity have increased risk of medical and obstetric complications during pregnancy, often leading to a recommendation for induction of labor (IOL). Misoprostol is commonly used for IOL, however there is limited data on whether it’s pharmacokinetics (PK) are altered by body size. The objective of this study is to evaluate PK parameters of oral misoprostol in pregnancies complicated by obesity. Pilot, single-center, observational study of non-fasting, term, singleton pregnancies with body mass index (BMI) > 30.0 kg/m2 at time of IOL with 50 mcg oral misoprostol. Plasma concentrations of active metabolite misoprostol acid (MPA) were measured at four time points using liquid chromatography mass spectrometry. Plasma MPA-time data analyzed using a non-compartmental PK model to derive the area under the curve from the first time point to the last measured concentration (AUC0-t) using the trapezoidal rule. Terminal slope (λz) used to extrapolate plasma concentration to infinity (AUC0-∞). Maximum serum concentration (Cmax) and time to maximum plasma concentration (Tmax) also described. 26 plasma observations from 7 subjects were included (Table 1). Observed plasma concentrations over time (Figure 1) demonstrate median(range) Cmax 26.63 (7.18-56.24) pg/mL, AUC0-t 10.93 (2.43-24.64) pg-h/mL, λz 2.68 (2.00-3.07) h-1, AUC0-∞ 22.67 (12.09-30.60) pg-h/mL. Tmax observed at 0.25 hours. Prior study evaluating 50 mcg oral misoprostol in 12 subjects with normal BMI (mean 28.6 kg/m2) reports mean±SD Cmax 53.97±23.79 pg/mL, AUC0-t 55.02±28.80 pg-h/mL, λz 1.05±0.86 h-1, AUC0-∞ 66.63±33.22 pg-h/mL, Tmax 0.23±0.14 hours. To our knowledge, this study is the first examination of 50 mcg oral misoprostol PK parameters among parturients with obesity undergoing term IOL. Data show decreases in PK parameters in this population, however some results are still within reported margin of error and there is marked variance between subjects. A future, powered, comparative trial is necessary to confirm these findings as well as further investigate clinically relevant outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)