Zonisamide serum concentrations during pregnancy

Arne Reimers; Grethe Helde; Noémi Becser Andersen; Dag Aurlien; Elisabeth Surlien Navjord; Kathrine Haggag; Jakob Christensen; Kari Mette Lillestølen; Karl Otto Nakken; Eylert Brodtkorb

doi:10.1016/j.eplepsyres.2018.05.002

Zonisamide serum concentrations during pregnancy

Epilepsy Res. 2018 Aug:144:25-29. doi: 10.1016/j.eplepsyres.2018.05.002. Epub 2018 May 4.

Affiliations

¹ Dept. of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway; Dept. of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Electronic address: arne.reimers@stolav.no.
² Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
³ Dept. of Neurology, The Neuroscience Center, Copenhagen University Hospital, Copenhagen, Denmark.
⁴ Dept. of Neurology, Stavanger University Hospital, Stavanger, Norway.
⁵ Dept. of Neurology, Drammen Hospital, Drammen, Norway.
⁶ Dept. of Neurohabilitation, Oslo University Hospital, Ullevål, Norway.
⁷ Dept. of Neurology, Aarhus University Hospital, Aarhus, Denmark.
⁸ The National Center for Epilepsy, Oslo University Hospital, Sandvika, Norway.
⁹ Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Dept. of Neurology and Clinical Neurophysiology, St. Olavs University Hospital, Trondheim, Norway.

PMID: 29751353
DOI: 10.1016/j.eplepsyres.2018.05.002

Abstract

Purpose: To investigate the change in zonisamide (ZNS) serum concentration and its consequences in pregnant women with epilepsy.

Methods: Six hospitals in Norway and Denmark screened their records for women who had been using ZNS during pregnancy. Absolute serum concentrations as well as concentration/dose (CD)-ratios were compared to non-pregnant values. Descriptive data on seizure control and obstetrical data were also collected.

Results: 144 serum concentrations from 23 pregnancies in 15 individual women with epilepsy were included (six on monotherapy). The mean ZNS serum concentration fell to a minimum of 58.6 ± 15.1%, while the C/D-ratio fell to as low as 55.1 ± 15.3% of the non-pregnant-value. The lowest values were seen in gestational months six to nine, and the individual nadir varied considerably (range: 24-81% of the non-pregnant value). Four out of ten previously seizure-free patients experienced breakthrough seizures. Gestational age, weight at birth and head circumference of the newborns were within the reference ranges.

Conclusions: ZNS serum concentrations may fall by over 40% during pregnancy, with large interindividual variability. In some patients, this may lead to worsened seizure control. These findings are in line with reports on other AEDs and suggest that regular therapeutic drug monitoring and dose adjustments may be useful.

Keywords: Antiepileptic drug; Elimination; Epilepsy; Pharmacokinetics; Pregnancy; Serum concentration; Zonisamide.

Publication types

Multicenter Study

MeSH terms

Adult
Denmark
Drug Monitoring / methods*
Epilepsy / blood*
Epilepsy / drug therapy*
Female
Gestational Age
Humans
Norway
Pregnancy
Pregnancy Complications / chemically induced
Young Adult
Zonisamide / blood*
Zonisamide / therapeutic use*

Substances

Zonisamide