Abstract：OBJECTIVE To evaluate the pharmacokinetic changes of lamotrigine from pre-pregnancy to postpartum in a Chinese population, to assess the correlation between the changes of serum lamotrigine concentration during pregnancy and epileptic seizure frequency, and to determine the predictors of the increased seizure frequency during pregnancy. METHODS The clinical records of pregnant women with epilepsy who were treated with lamotrigine monotherapy and had regular therapeutic drug monitoring in the Department of Neurology, Shengjing Hospital of China Medical University from January 2016 to November 2019 were collected. The apparent clearance (CL/F) and the ratio to target concentration (RTC) were calculated for each trimester or for each month. RTCs were compared between patients with and without an increase in the frequency of seizures to evaluate the correlation between the changes of serum lamotrigine concentration during pregnancy and epileptic seizure frequency. A receiver operating characteristic (ROC) curve was drawn to determine the threshold of RTC and to predict the increased seizure frequency. RESULTS A total of 23 patients contributing to 282 blood samples were reviewed retrospectively. CL/F increased by 105.23% during the first trimester (P=0.001 4), 202.85% during the second trimester (P<0.000 1), and 201.11% during the third trimester (P<0.000 1) compared with the pre-pregnancy level. The value decreased rapidly on the day of delivery and gradually returned to the pre-pregnancy level at 6 weeks after delivery. Ten patients who had adequate baseline information were included to examine the association between serum lamotrigine concentration and seizure frequency. The RTC values of patients with and without an increased seizure frequency were significantly different (P<0.000 1), and increased seizure frequency was associated with a lower RTC. An RTC<0.62 was a predictor of deteriorating seizures. CONCLUSION The pharmacokinetic changes in lamotrigine during pregnancy display significant inter-individual variation. Constant vigilance is necessary in order to avoid epileptic seizures for women with epilepsy on lamotrigine monotherapy during pregnancy when the lamotrigine serum concentration is less than 62% of the target concentration. Therapeutic drug monitoring can support a rational treatment plan for lamotrigine use during pregnancy.
王鸣璐, 李惟滔, 陶玉瑛, 谭小平, 郭阳, 肇丽梅. 妊娠期拉莫三嗪血药浓度变化及与发作频率相关性研究[J]. 中国药学杂志, 2021, 56(2): 128-134.
WANG Ming-lu, LI Wei-tao, TAO Yu-ying, TAN Xiao-ping, GUO Yang, ZHAO Li-mei. Changes of Serum Lamotrigine Concentration during Pregnancy and Its Correlation with Epileptic Seizure Frequency. Chinese Pharmaceutical Journal, 2021, 56(2): 128-134.
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