Abstract Details

Title Maternal Symptomatic Toxicity and Oxcarbazepine Free Fraction during Pregnancy in Women with Epilepsy

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S13 - Epilepsy/Clinical Neurophysiology (EEG): Antiseizure Medications (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

Background

We observed women in our epilepsy-obstetrics practice developing symptomatic toxicity late in pregnancy when oxcarbazepine dose adjustments were made to maintain the baseline target concentration. Free fraction of carbamazepine increases during pregnancy, but free fraction has not been evaluated for oxcarbazepine, which is only moderately protein-bound.

Objective

To investigate gestational-induced changes in the free fraction of oxcarbazepine.

Design/Methods The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multi-center investigation of pregnant women with epilepsy (PWWE). Blood was collected during 4 visits in pregnancy and 3 postpartum. Postpartum was used as the comparator non-pregnant state. For women on oxcarbazepine, total and unbound serum concentrations of the monohydroxyderivative of oxcarbazepine (MHD) were measured. Free fraction was calculated by dividing the unbound by total MHD concentrations. All concentrations and free fractions for an individual were combined for trimester 3 (TM3) and for postpartum. Mean values for TM3 and postpartum were compared using paired t test in R (version 4.1.0) with a significance level of p<0.05.

Results

Twenty PWWE on oxcarbazepine had total and free MHD plasma concentrations measured in the MONEAD Core Lab, with 13 PWWE having concentrations in both TM3 and postpartum. Within an individual woman the free fraction was on average higher in TM3 than postpartum (0.56±0.12 versus 0.51±0.15) (p=0.01). Notably, the total MHD concentrations were lower in TM3 compared to postpartum (13.3±7.4 versus 16.0±7.0) (p=0.01), whereas the unbound (free) concentrations were stable (7.9±5.5 versus 8.6±5.4) (p=0.31).

Conclusions

The free fraction of MHD is higher in the 3^rd trimester of pregnancy compared to non-pregnant baseline. Adjusting oxcarbazepine dosages during pregnancy to maintain the individualized baseline target concentration based on total MHD serum concentrations may result in maternal symptomatic toxicity and undue fetal over-exposure to oxcarbazepine. Free MHD concentrations should be made available for therapeutic drug monitoring use during pregnancy.

Authors/Disclosures
Page B. Pennell, MD, FAAN (University of Pittsburgh School of Medicine) PRESENTER	The institution of Dr. Pennell has received research support from NIH. The institution of an immediate family member of Dr. Pennell has received research support from Department of Defense. The institution of an immediate family member of Dr. Pennell has received research support from Environmental Protection Agency. The institution of an immediate family member of Dr. Pennell has received research support from NIH. The institution of an immediate family member of Dr. Pennell has received research support from Advanced Energy Consortium. Dr. Pennell has received publishing royalties from a publication relating to health care.
Angela K. Birnbaum, PhD (University of Minnesota)	The institution of Dr. Birnbaum has received research support from National Institutes of Health. The institution of Dr. Birnbaum has received research support from Randy Shaver Cancer and Research Foundation. Dr. Birnbaum has received intellectual property interests from a discovery or technology relating to health care.
Charul Avachat	Miss Avachat has nothing to disclose.
Sean Hwang, MD (Hofstra Northwell School of Medicine)	Dr. Hwang has nothing to disclose.
Laura A. Kalayjian, MD (University of Southern California)	The institution of Dr. Kalayjian has received research support from NIH.
Elizabeth Gerard, MD (Northwestern University)	Dr. Gerard has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich Pharmaceuticals. The institution of Dr. Gerard has received research support from NIH/NINDS. The institution of Dr. Gerard has received research support from Xenon Pharmaceuticals. The institution of an immediate family member of Dr. Gerard has received research support from NIH. The institution of an immediate family member of Dr. Gerard has received research support from Novo Nordisk. The institution of Dr. Gerard has received research support from Eisai, Inc. (via Stanford University).
Abigail Matthews (The Emmes Company, LLC)	No disclosure on file
Carrie Brown (Emmes)	No disclosure on file
Kimford J. Meador, MD, FAAN (Stanford University School of Medicine)	The institution of Dr. Meador has received research support from NIH. The institution of Dr. Meador has received research support from Eisai. The institution of Dr. Meador has received research support from Medtronics. The institution of Dr. Meador has received research support from The Epilepsy Consortium.