Michael Paulzen1, Tamme W Goecke2, Elmar Stickeler2, Gerhard Gründer3, Georgios Schoretsanitis4. 1. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, JARA - Translational Brain Medicine, Aachen, Germany. Electronic address: mpaulzen@ukaachen.de. 2. Department of Gynecology and Obstetrics, RWTH Aachen University, Germany. 3. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, JARA - Translational Brain Medicine, Aachen, Germany. 4. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, JARA - Translational Brain Medicine, Aachen, Germany; University Hospital of Psychiatry, Bern, Switzerland.
Abstract
RATIONALE: This study is the first to measure and correlate sertraline concentrations in maternal blood, amniotic fluid and umbilical cord blood and account for distribution of the drug between these three compartments. METHODS: Concentrations of sertraline were measured in six mother infant pairs at the time of delivery. Data are provided as median values, first and third quartiles as well as ranges. To account for the penetration ratio into amniotic fluid and cord blood, the concentration of sertraline in both environments was divided by the concentration in maternal serum. Daily doses were correlated with maternal serum- and umbilical cord blood-concentrations, and serum levels were correlated with levels in amniotic fluid. RESULTS: The median daily dose of sertraline was 75mg (Q1: 43.75mg, Q3: 100mg; range 25-100mg). Amniotic fluid concentrations of sertraline strongly correlated with the daily dose (r=0.833, p=0.039) while neither maternal serum concentrations nor cord blood concentrations correlated with the daily dose (p>0.05). The median penetration ratio for sertraline into amniotic fluid was 0.57 (Q1: 0.28, Q3: 0.75; range: 0.22-0.88). The median penetration ratio into the fetal circulation, calculated on the basis of umbilical cord blood-concentrations, was found to be 0.36 (Q1: 0.28, Q3: 0.49; range: 0.17-0.65). CONCLUSIONS: Sertraline concentrations in amniotic fluid gave evidence that maternally administered sertraline is constantly accessible to the fetus via amniotic fluid in a manner not previously appreciated. A relatively low penetration into fetal circulation may contribute to a sufficient safety profile of sertraline during pregnancy although in our study APGAR Scores were relatively low in three infants. Our data support the important role of therapeutic drug monitoring in maintaining the safety of pregnant women and exposed infants.
RATIONALE: This study is the first to measure and correlate sertraline concentrations in maternal blood, amniotic fluid and umbilical cord blood and account for distribution of the drug between these three compartments. METHODS: Concentrations of sertraline were measured in six mother infant pairs at the time of delivery. Data are provided as median values, first and third quartiles as well as ranges. To account for the penetration ratio into amniotic fluid and cord blood, the concentration of sertraline in both environments was divided by the concentration in maternal serum. Daily doses were correlated with maternal serum- and umbilical cord blood-concentrations, and serum levels were correlated with levels in amniotic fluid. RESULTS: The median daily dose of sertraline was 75mg (Q1: 43.75mg, Q3: 100mg; range 25-100mg). Amniotic fluid concentrations of sertraline strongly correlated with the daily dose (r=0.833, p=0.039) while neither maternal serum concentrations nor cord blood concentrations correlated with the daily dose (p>0.05). The median penetration ratio for sertraline into amniotic fluid was 0.57 (Q1: 0.28, Q3: 0.75; range: 0.22-0.88). The median penetration ratio into the fetal circulation, calculated on the basis of umbilical cord blood-concentrations, was found to be 0.36 (Q1: 0.28, Q3: 0.49; range: 0.17-0.65). CONCLUSIONS:Sertraline concentrations in amniotic fluid gave evidence that maternally administered sertraline is constantly accessible to the fetus via amniotic fluid in a manner not previously appreciated. A relatively low penetration into fetal circulation may contribute to a sufficient safety profile of sertraline during pregnancy although in our study APGAR Scores were relatively low in three infants. Our data support the important role of therapeutic drug monitoring in maintaining the safety of pregnant women and exposed infants.
Authors: Michael Paulzen; Julia C Stingl; Marc Augustin; Helena Saßmannshausen; Cordula Franz; Gerhard Gründer; Georgios Schoretsanitis Journal: Clin Pharmacokinet Date: 2019-04 Impact factor: 6.447
Authors: Georgios Schoretsanitis; Andreas A Westin; Julia C Stingl; Kristina M Deligiannidis; Michael Paulzen; Olav Spigset Journal: Prog Neuropsychopharmacol Biol Psychiatry Date: 2021-01-02 Impact factor: 5.067
Authors: E Heinonen; M Blennow; M Blomdahl-Wetterholm; M Hovstadius; J Nasiell; A Pohanka; L L Gustafsson; K Wide Journal: Eur J Clin Pharmacol Date: 2021-03-22 Impact factor: 2.953