Pharmacokinetic Changes and Seizure Outcomes in Pregnant Women Taking Second-Generation Antiepileptic Drugs

Purpose The study aims to investigate pharmacokinetic alterations in second-generation antiepileptic drugs (AEDs) and evaluate the relationship between drug blood concentration fluctuations and the seizure control deterioration in pregnant women. Methods A prospective study was conducted in 52 pregnancies with epilepsy. Clinical data of participants including oral daily doses and seizure frequency were acquired from the patients’ routine clinical practice. Blood AEDs concentrations obtained via therapeutic drug monitoring(TDM) were used to calculate apparent oral clearance at preconception and each trimester during pregnancy. Clearane changes were assessed between non-pregnant baseline and gestational trimesters. The ratio of AEDs concentration to the individual preconception baseline concentration (RTC) in each trimester was compared between patients experiencing seizure deterioration and those maintaining stability. Moreover, receiver operating characteristic (ROC) curve predicted the threshold RTC for increased seizure frequency. Results The apparent oral clearance of levetiracetam (LEV) and lamotrigine (LTG) showed a significant increase across all trimesters versus 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(Cl) increase during the third trimester, reaching 1.6 times baseline values (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, apparent oral clearance and blood level of oxcarbazepine (OXC) remained stable throughout gestation compared to preconception baseline. Moreover, RTC values significantly differed between participants with and without seizure deterioration for all three AEDs, indicating lower RTCs were associated with seizure worsening. Conclusion Significant pharmacokinetic fluctuations in LEV and LTG were observed in Chinese pregnant women. Our study validated the necessity of early therapeutic drug monitoring of newer AEDs and dose adjustments to maintain blood concentrations near non-pregnant baselines for pregnant women with epilepsy.