Pharmacokinetics of Antiepileptic Drugs During Pregnancy

Pregnancy induces profound physiological changes that alter the absorption, distribution, metabolism and excretion of antiepileptic drugs (AEDs). Expanded plasma volume and increased body water lead to a larger volume of distribution, while elevated hepatic enzyme activity and enhanced renal blood flow accelerate drug clearance. As a result, serum concentrations of widely used AEDs—such as lamotrigine, levetiracetam and oxcarbazepine—can fall substantially during the second and third trimesters. These pharmacokinetic shifts carry clinical consequences: subtherapeutic levels may precipitate breakthrough seizures with attendant risks to mother and foetus, whereas abrupt postpartum normalization of clearance may lead to toxicity if doses are not promptly adjusted. Therapeutic drug monitoring (TDM) is therefore integral to optimising seizure control throughout gestation, guiding dose increments in pregnancy and tapering after delivery. Understanding drug-specific patterns of change and interindividual variability underpins personalised management, balancing the need to maintain maternal health against the imperative to minimise fetal exposure and developmental risk.

Research from Nature Portfolio

Preclinical investigations into the third-generation AED lacosamide have characterised its distribution in maternal and embryonic compartments and linked exposure levels to developmental outcomes. In a murine model, lacosamide and its metabolites were quantified in maternal serum and embryonic tissues using high-resolution mass spectrometry. Data revealed rapid placental transfer, with embryonic concentrations approximating those of the dam, and a dose-dependent increase in foetal malformations and perinatal lethality. Subsequent histological and behavioural assessments of offspring uncovered neurodevelopmental alterations in cortical and limbic regions analogous to those observed in schizophrenia spectrum disorders. These findings underscore the importance of delineating tissue-specific pharmacokinetics of newer AEDs to anticipate teratogenic potential and inform safer therapeutic regimens during human pregnancy.

Pharmacokinetics of Antiepileptic Drugs During Pregnancy publication trend

The graph below shows the total number of articles in pharmacokinetics of antiepileptic drugs during pregnancy across all publications each year (not limited to Nature Index journals).

Technical terms

Pharmacokinetics: The study of how drugs are absorbed, distributed, metabolised and excreted by the body.

Clearance: The volume of plasma from which a drug is completely removed per unit of time, reflecting elimination efficiency.

Volume of distribution: A theoretical volume that describes how a drug disperses throughout body compartments relative to plasma concentration.

Therapeutic drug monitoring: The measurement of specific drug levels in biological fluids to guide dose adjustments and ensure efficacy and safety.

Transplacental transfer: The movement of substances across the placental barrier from maternal to foetal circulation.

Dose-adjusted concentration: The ratio of drug concentration in plasma to the administered dose, allowing comparison across individuals and timepoints.

References

1. The impact of pregnancy on the pharmacokinetics of antiseizure medications: A systematic review and meta-analysis of data from 674 pregnancies. Progress in Neuro-Psychopharmacology and Biological Psychiatry (2024).
2. Model‐based lamotrigine clearance changes during pregnancy: clinical implication. Annals of Clinical and Translational Neurology (2014).
3. Lacosamide intake during pregnancy increases the incidence of foetal malformations and symptoms associated with schizophrenia in the offspring of mice. Scientific Reports (2020).
4. Management of Anti-Seizure Medications during Pregnancy: Advancements in The Past Decade. Pharmaceutics (2022).