Effects of maternal obesity on the pharmacokinetics of vaginal misoprostol during induction of labor

Abstract

Obesity has reached epidemic proportions worldwide. Over 40% of pregnant women who are starting pregnancy today are obese or overweight. Obese women are more susceptible to medical, surgical and obstetric complications such as higher rates of induction of labor and failed induction. Misoprostol is a synthetic prostaglandin E1 analogue used for inducing labor. This study aims to evaluate the influence of maternal obesity on the pharmacokinetics of misoprostol in pregnant women. The study also reports the evaluation of transplacental distribution of misoprostol acid and its concentration in amniotic fluid and breast milk. Divided into four groups, 140 pregnant women will be investigated: 35 non-obese; 35 with obesity grade 1; 35 with obesity grade 2; 35 with morbid obese. In all patients will be studied genotype, polymorphism and expression of P-gp and in 10 parturients from each group will be studied the pharmacokinetics and placental transfer of misoprostol. After admission and signature of the consent form and before the administration of 25µg vaginal misoprostol tablet, vaginal pH will be measured and serial blood samples will be collected at times zero, 1, 2, 5, 10, 20 , 30, 45, 60, 120, 240, 300, 360 minutes. At birth, samples of maternal and fetal blood will be collected to genotype and to determine the rate of placental transfer. Aliquots of blood from the intervillous space, amniotic fluid and breast milk will also be collected. After the collection of biological samples, chromatographic analyzes will be performed to determine plasma concentrations of misoprostol acid and, consequently, to evaluate the pharmacokinetic parameters and the rate of placental transfer. The SNPs of the MDR1 gene, related to changes in P-glycoprotein (P-gp) activity, will be genotyped by polymerase chain reaction in real time using allelic discrimination assays. The placental mRNA expression of ABCB1 gene and its product, P-gp (sincitiotrofoblasto collection), will be analyzed using the techniques of RT-PCR and immunohistochemistry. (AU)