The PBPK Study

Physiological-based Pharmacokinetics Approach to Determine the Extent of Drug Exposure of Anti-seizure Medications During Pregnancy and Breastfeeding

This project focuses on anti-seizure medication (ASM) clearance and physiological factors determining blood concentrations in pregnant adult women with epilepsy and amounts of exposure to their unborn children and nursing infants.

Project Members

  • Page B. Pennell, MD, FAES -- Principal Investigator
  • Arundhathi Jeyabalan, MD, MSCR -- Co-Investigator
  • Kerri Oddis, Nikhil Khonbantabam -- Research Coordinator(s)
  • Erica Kemp, PA-C -- Research PA

This study aims to gather additional information to fill in gaps of knowledge. Specific variables that were not studied in MONEAD (Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs) will be addressed in this study. Specifically, MONEAD, lacked early pregnancy data/sampling because enrollment for the study was up to 20 weeks. This study will enroll women pre-conception. Additionally, there was a lack of early postpartum data, so this study will attempt to close that gap and obtain more frequent sampling during critical windows of rapid pharmacokinetic changes.  Participants will be followed on a schedule similar to MONEAD but with more frequent sampling.

This study will enroll a total of 60 participants on 1 of 2 medications, levetiracetam and/or lamotrigine. Many prior clinical studies have demonstrated the safety of these 2 medications during pregnancy. This is purely an observational study, and the participants clinical care will not be altered.

The study will consist of 6 visits spanning pre-conception to delivery to post-partum. Data consisting of various questionnaires, surveys, and blood/urine/breast milk samples will be collected.

Goal

The goal of this project is to develop modeling of pharmacokinetic changes for these two ASMs during pregnancy and postpartum that can be used to adjust doses in practice without obtaining frequent visits to the lab for therapeutic drug monitoring; and predict exposure of less frequently prescribed ASMs in mothers and their infants in order to maintain the individualized target concentrations, thus protecting mothers from seizure worsening and minimizing fetal toxicity.