MATERIAL AND METHODS
This study included 126 patients of medicine abortion from December 2019 to November 2020 in Fujian Maternity and Child Health Hospital. The participants should meet the following criteria: (a) gestational age ≤ 49 days; (b) intra-uterine pregnancy; (c) the absence of contraindication for using either mifepristone and misoprostol, such as hemorrhagic disorders, liver dysfunction and concurrent anticoagulant therapy. The patients treated with CYP3A4 inhibitor or inducer were excluded in case of impaction on the blood concentration of mifepristone. These patients received oral 100 mg mifepristone for two days and followed with oral 600 mg misoprostol at the third day. All participants gave informed consent to undergo medical abortion. The ethical approval of this study was obtained from clinical research ethics committee of Fujian Maternity and Child Health Hospital (2020KY135).
Blood sample was collected into EDTA tube before oral misoprostol at the third day morning. The concentration of mifepristone and its monodemethylated metabolite were determined by LC-MS/MS analysis using electro-spray ionization (ESI) in the multiple reaction monitoring (MRM) mode.16
Clinical outcome was evaluated based on complete expulsion of intrauterine contents with or without surgical intervention. Meanwhile, the adverse drug reactions of mifepristone were recorded, including dizziness, hypogastralgia, metrorrhagia, nausea and vomiting. Blood concentration (C) / dose ratios (C/D) as an index of mifepristone pharmacokinetics were the dose-adjusted mifepristone and its monodemethylated metabolites concentration, which was calculated by C (ng/mL) over the dose of mifepristone per kilogram weight (mg/kg) in corresponding 24 h.
5 mL of whole blood samples was collected for the DNA extraction. DNA was isolated by using a kit (Qiagen, Germany) according to the manufacturer’s protocol, and stored at −20 °C until analysis. Genotyping of MDR1 and CYP3A4 were performed using the Sequenom MassARRAY iPLEX platform (Agena Bioscience, San Diego, CA, USA).
Categorical variables, such as successful cases of medical abortion and cases who suffered from adverse reactions, were compared by χ2 tests. Continuous variables, such as blood concentration was compared by one-way analysis of variance. Hardy-Weinberg equilibrium was tested by χ2 tests to compare expected frequencies of genotypes and observed values. Pvalue < 0.05 with two-sided was considered statistically significant. Data were performed by SPSS Statistics (Version 22.0, SPSS Inc., Chicago, IL, USA).