Pharmacokinetic changes and seizure outcomes in pregnant women taking second-generation antiseizure medications

BACKGROUND: Effective seizure management in pregnant women with epilepsy poses significant clinical challenges. This study aimed to investigate the pharmacokinetic changes of second-generation antiseizure medications (ASMs) and their association with the deterioration of seizure control in Han Chinese women with epilepsy. METHODS: Patient clinical data including oral daily doses and seizure frequency were acquired from routine clinical practice. Blood concentrations of ASMs determined by therapeutic drug monitoring (TDM) were used to calculate apparent oral clearance (CL) at preconception and each trimester during pregnancy. The ratio of ASM concentration in each trimester to the preconception baseline concentration (RTC) was compared between patients experiencing seizure deterioration and those maintaining stability. Moreover, receiver operating characteristic (ROC) curve analysis was used to identify the threshold RTC value predicting increased seizure frequency. RESULTS: A total of 52 pregnant patients with epilepsy were initially enrolled in this study. The apparent oral clearance of levetiracetam (LEV) and lamotrigine (LTG) showed a significant increase across all trimesters compared to the nonpregnant baseline. Peak clearance occurred in the third trimester for LTG with a 2.0-fold relative clearance (P < 0.05). Similarly, LEV displayed maximum apparent oral clearance increase during the third trimester, reaching 1.6 folds of baseline value (P < 0.05). As a result, serum concentrations of LEV and LTG significantly decreased during pregnancy compared to non-pregnant baseline levels (P < 0.05). However, the apparent oral clearance and the blood level of oxcarbazepine (OXC) remained stable throughout gestation compared to the preconception baseline. Moreover, the RTC values significantly differed between participants with and without seizure deterioration for all three ASMs, indicating that lower RTCs were associated with seizure worsening. CONCLUSIONS: Our study revealed significant pharmacokinetic fluctuations of LEV and LTG in Chinese pregnant women. This highlights the necessity of early therapeutic drug monitoring for newer ASMs and dose adjustments to maintain blood concentrations near the non-pregnant baseline level in pregnant women with epilepsy.