Gestational Changes in Antiseizure Medication Concentrations and the Impact of Polytherapy

BACKGROUND AND OBJECTIVES: Pregnancy alters the pharmacokinetics of antiseizure medications (ASMs). The aim of this study was to quantify gestational changes in ASM concentrations and identify independent covariates among women with epilepsy in China. METHODS: In this prospective, multicenter observational cohort study in China, women with epilepsy aged 18-45 years were enrolled and followed longitudinally. Steady-state trough ASM concentrations were measured, with concentration-to-dose (C/D) ratio as the primary pharmacokinetic parameter. Linear mixed-effects models with model averaging were used to evaluate the independent effects of gestational age, concomitant ASMs, and demographic covariates on ASM C/D ratios. Perampanel showed an increasing trend but was limited by sample and polytherapy. Concomitant ASMs primarily shifted baseline C/D ratios without altering gestational changes, and several drug-drug interactions were identified. Higher body weight was associated with lower C/D ratios for most ASMs, except for perampanel. Interindividual variability remained the dominant factor determining C/D ratios over measured covariates. DISCUSSION: Pregnancy was the primary driver of declining C/D ratios, and concomitant ASMs and body weight acted as secondary modifiers. These findings support individual therapeutic drug monitoring. TRIAL REGISTRATION INFORMATION: ChiCTR2100046318 (Chinese Clinical Trial Registry, chictr.org.cn).