Michael Paulzen1,2,3, Julia C Stingl4,5, Marc Augustin2,3, Helena Saßmannshausen6, Cordula Franz6, Gerhard Gründer7, Georgios Schoretsanitis8,9,10. 1. Alexianer Hospital Aachen, Aachen, Germany. 2. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074, Aachen, Germany. 3. JARA-Translational Brain Medicine, RWTH Aachen University, 52074, Aachen, Germany. 4. Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany. 5. Centre for Translational Medicine, University Bonn Medical Faculty, Bonn, Germany. 6. Department of Gynecology and Obstetrics, RWTH Aachen University, Aachen, Germany. 7. Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 8. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074, Aachen, Germany. george.schor@gmail.com. 9. JARA-Translational Brain Medicine, RWTH Aachen University, 52074, Aachen, Germany. george.schor@gmail.com. 10. University Hospital of Psychiatry, Bolligenstrasse 111, 3000, Bern, Switzerland. george.schor@gmail.com.
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.
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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