Pharmacokinetic changes for newer antiepileptic drugs and seizure control during pregnancy

Abstract

Objective: To investigate pharmacokinetic changes in newer antiepileptic drugs (AEDs) and assess seizure frequencies and risk factors of increased seizures during pregnancy in women with epilepsy (WWE). Methods: A total of 56 pregnancies in 53 WWE who received newer antiepileptic drugs (AEDs) were enrolled. Data on seizure activity and types, daily dose, and AEDs blood levels were derived from routine clinical follow-up. Changes in AEDs clearance were compared between each trimester and nonpregnant baseline. The ratio of AED levels of each trimester to their targets (nonpregnant baseline) concentrations (RTC) was compared between patients with and without an increased seizure. A binary logistic regression was used to investigate the risk factors contributing to seizure worsening during pregnancy. Results: Increased clearances of LTG, LEV, and OXC were observed in all trimesters versus nonpregnant baseline. The peak changes in the clearance of LTG (3.42-fold baseline clearance) (p < 0.001) and LEV (2.78-fold) (p < 0.001) occurred in the second trimester during pregnancy, followed by oxcarbazepine (2.11-fold) in the third trimester (p < 0.03). Plasma concentrations of LTG and LEV during pregnancy were significantly decreased compared to baseline levels, except for OXC. However, no significant differences in RTC values were observed between patients with and without seizure worsening. Some risk factors as seizures for the prior nine months could significantly affect seizure frequency during pregnancy. Conclusion: We found substantial changes in the pharmacokinetics of multiple newer AEDs in WWE, reinforcing the need for therapeutic drug monitoring (TDM) during pregnancy. We would encourage at least one monitoring every trimester and probably more frequently for women with poorly seizure control before pregnancy, and AEDs dose adjustment should keep up with clearance changes. In addition, a well-controlled seizure nine months before pregnancy could lower the risks of seizure during pregnancy, highlighting the importance of pre-pregnancy counseling and seizure management before pregnancy.