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Comprehensive Measurements of Intrauterine and Postnatal Exposure to Lamotrigine

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Abstract

Objective

The aim of this study was to measure and investigate correlations of lamotrigine concentrations in maternal as well as umbilical cord blood, amniotic fluid, and breast milk to account for the distribution of the drug.

Methods

Concentrations of lamotrigine were measured in 19 mother–infant pairs at the time of delivery. To account for the penetration ratio into amniotic fluid, cord blood and breast milk, the concentration of lamotrigine in the particular environment was divided by the concentration in maternal serum. A no-intercept model was applied for associations between maternal serum concentrations, amniotic fluid, umbilical cord blood, and breast milk concentrations.

Results

The mean daily dosage of lamotrigine was 351.32 mg (range 50–650 mg). We detected associations between maternal serum and amniotic fluid (β = 0.088, p < 0.001), as well as umbilical cord (β = 0.939, p < 0.001) and breast milk (β = 0.964, p < 0.001). The median penetration ratio into amniotic fluid, cord blood, and breast milk was 0.68, 0.92, and 0.77, respectively.

Conclusions

Lamotrigine concentrations in amniotic fluid, cord blood, and breast milk give evidence that the fetus/newborn is constantly exposed to lamotrigine. Maternal serum concentrations predicted exposure via amniotic fluid, umbilical cord, and breast milk. Data suggest that therapeutic drug monitoring can be recommended as part of the clinical routine in psychopharmacotherapy for pregnant or breastfeeding women.

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Acknowledgements

The authors wish to express their gratitude to the number of people from the Department of Gynaecology and Obstetrics, RWTH Aachen University who support the ongoing study by identifying pregnant women medicated with psychotropic drugs. Our appreciation is given to the wonderful team of midwifes and to Dr. Rebecca Caspers, MUDr. Tomáš Kupec, and Bartlomiej Berger.

Author information

Authors and Affiliations

  1. Alexianer Hospital Aachen, Aachen, Germany

    Michael Paulzen

  2. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074, Aachen, Germany

    Michael Paulzen, Marc Augustin & Georgios Schoretsanitis

  3. JARA-Translational Brain Medicine, RWTH Aachen University, 52074, Aachen, Germany

    Michael Paulzen, Marc Augustin & Georgios Schoretsanitis

  4. Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany

    Julia C. Stingl

  5. Centre for Translational Medicine, University Bonn Medical Faculty, Bonn, Germany

    Julia C. Stingl

  6. Department of Gynecology and Obstetrics, RWTH Aachen University, Aachen, Germany

    Helena Saßmannshausen & Cordula Franz

  7. Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Gerhard Gründer

  8. University Hospital of Psychiatry, Bolligenstrasse 111, 3000, Bern, Switzerland

    Georgios Schoretsanitis

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  1. Michael Paulzen
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Correspondence to Georgios Schoretsanitis.

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Author contributions

Drs. Saßmannshausen, Franz, Schoretsanitis, Stingl, Augustin, Gründer, and Paulzen participated in the research design of the study. Drs. Schoretsanitis and Paulzen performed the initial statistical analyses. Dr. Schoretsanitis and Dr. Paulzen wrote the first article draft. All authors contributed to the interpretation of data and approved the final manuscript.

Funding

No commercial organizations had any role in the completion or publication of this study. Dr. Schoretsanitis received a grant from the bequest “in memory of Maria Zaoussi”, State Scholarships Foundation, Greece, for clinical research in psychiatry for the academic year 2015–2016.

Conflict of interest

Gerhard Gründer has served as a consultant for Allergan (Dublin, Ireland), Boehringer Ingelheim (Ingelheim, Germany), Eli Lilly (Indianapolis, IN, USA), Janssen-Cilag (Neuss, Germany), Lundbeck (Copenhagen, Denmark), Ono Pharmaceuticals (Osaka, Japan), Otsuka (Chiyoda, Japan), Recordati (Milan, Italy), Roche (Basel, Switzerland), Servier (Paris, France), and Takeda (Osaka, Japan). He has served on the speakers’ bureau of Eli Lilly, Janssen Cilag, Neuraxpharm (Langenfeld, Germany), Lundbeck, Otsuka, Recordati, Roche, Servier, and Trommsdorf (Aachen, Germany). He has received grant support from Boehringer Ingelheim and Roche. He is co-founder of Mind and Brain Institute GmbH (Zornheim, Germany) and Brainfoods GmbH (Zornheim, Germany). He reports no conflict of interest with this publication. Michael Paulzen, Julia C. Stingl, Marc Augustin, Helena Saßmannshausen, Cordula Franz, and Georgios Schoretsanitis had no conflicts of interest during the last 12 months.

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Paulzen, M., Stingl, J.C., Augustin, M. et al. Comprehensive Measurements of Intrauterine and Postnatal Exposure to Lamotrigine. Clin Pharmacokinet 58, 535–543 (2019). https://doi.org/10.1007/s40262-018-0713-y

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