Pregnancy exposure to venlafaxine-Therapeutic drug monitoring in maternal blood, amniotic fluid and umbilical cord blood and obstetrical outcomes
- PMID: 32056930
- DOI: 10.1016/j.jad.2020.02.010
Pregnancy exposure to venlafaxine-Therapeutic drug monitoring in maternal blood, amniotic fluid and umbilical cord blood and obstetrical outcomes
Abstract
Background: For treatment with psychotropic drugs during pregnancy, extended therapeutic drug monitoring is recommended for individual therapy adjustment. We measured venlafaxine (VEN), O-desmethylvenlafaxine (ODV) and active moiety, AM (sum of VEN+ODV) concentrations in maternal serum, amniotic fluid and umbilical cord blood.
Methods: Concentrations of VEN, ODVEN and AM were measured in nine mother-infant pairs at time of delivery; in five cases, amniotic fluid samples were available. Concentrations are reported as median values, first (Q1) and third (Q3) quartiles and ranges. Penetration ratio was calculated by dividing concentrations of VEN, ODVEN and AM in amniotic fluid and umbilical cord blood by maternal serum concentrations.
Results: Median daily dosage of venlafaxine was 75 mg (range 37.5-225 mg). There were no significant correlations between daily dose, maternal serum, umbilical cord blood and amniotic fluid concentrations. Median penetration ratio into amniotic fluid was 2.5 (range 0.56-4.48). Median penetration ratio into fetal circulation was 1.05 (range 0.62-2.08). Median concentration of AM was 223.8 ng/mL, range 33.9-338.0 ng/mL (maternal serum), 789.0 ng/mL, range 309-1052.5 ng/mL (amniotic fluid) and 291.0 ng/mL, range 21.1-448.4 ng/mL (cord blood).
Discussion: VEN, ODVEN and AM concentrations in maternal serum, amniotic fluid and umbilical cord blood indicate that the fetus might have been exposed to relatively high concentrations throughout pregnancy. High concentrations in amniotic fluid indicate an increased penetration into and/or accumulation within amniotic fluid and a decreased elimination out of amniotic fluid. Findings indicate that fetal in-utero exposition to venlafaxine is higher compared to other antidepressants.
Keywords: Amniotic fluid; Antidepressants; Cord blood; Depression; Pharmacokinetics; Placental transfer; Pregnancy; Therapeutic drug monitoring; Venlafaxine.
Copyright © 2020 Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest Gerhard Gründer has served as a consultant for Boehringer Ingelheim (Ingelheim, Germany), Cheplapharm (Greifswald, Germany), Eli Lilly (Indianapolis, Indiana, USA), Lundbeck (Copenhagen, Denmark), Ono Pharmaceuticals (Osaka, Japan), Roche (Basel, Switzerland), Servier (Paris, France), and Takeda (Osaka, Japan). He has served on the speakers’ bureau of Eli Lilly, Gedeon Richter (Budapest, Hungary), Janssen Cilag (Neuss, Germany), Lundbeck, Roche, Servier, and Trommsdorf (Aachen, Germany). He has received grant support from Boehringer Ingelheim and Roche. He is 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 received a speaker's fee from Neuraxpharm, Langenfeld, Germany. All other authors declare no conflicts of interest as well. The research study did not receive funds or support from any source.
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