Vaginal Misoprostol Pharmacokinetic Changes in Obese Parturient Women Who Presented Labor Induction Failure

Abstract

Clinical experience shows an increased duration of labor in obese parturient women. It is unclear if this population should receive the same dose of vaginal misoprostol for induction of labor as non‐obese parturient women. We investigate the influence of obesity on the pharmacokinetics and placental transfer of the metabolite misoprostol acid in parturient women. Parturient women (n = 40) were enrolled and received misoprostol 25 µg/6 h vaginally and were allocated into two groups according to the pre‐pregnancy body mass index (BMI <30 kg/m2 non‐obese, n = 18 or BMI >30 kg/m2 obese, n = 22) or according to the labor induction outcome (failure [n = 10] or success [n = 30]). Blood collection for pharmacokinetic study occurred after the first misoprostol dose. The pharmacokinetic parameters obtained in non‐obese parturient women were not statistically different from those obtained in obese group (P Value > .05). However, when the parturient women were grouped by the labor induction outcome, the failed labor induction group presented a higher (median [interquartile range]) BMI (44.4 [34.6‐47.9] vs 33.7 [28.9‐36.5] kg/m2) (P Value = .0017), lower Cmax (11.5 [4.82‐22.2] vs 22.8 [14.2‐30.8] pg/mL) (P Value = .0308) and not statistically different AUC0‐6 (31.8 [13.4‐61.5] vs 53.4 [35.4‐77.7]) pg·h/mL) (P Value = .0580) and tmax (2.50 [1.19‐4.25] vs 3.00 (1.88‐5.00) h (P Value = .3198) when compared with parturient women who presented successful labor induction. This data suggests a higher loading dose (higher volume of distribution) and unchanged maintenance dose (unchanged AUC0‐6) of misoprostol for this population. Further studies are required to investigate the efficacy and safety of higher misoprostol loading doses for this population.