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).