Alexianer Hospital Aachen, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; JARA-Translational Brain Medicine, Aachen, Germany.
The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, New York, USA; Hofstra Northwell School of Medicine, Hempstead, New York, USA; The Feinstein Institute for Medical Research, Manhasset, New York, USA.
J Affect Disord. 2020 Apr 1;266:578-584. doi: 10.1016/j.jad.2020.02.010. Epub 2020 Feb 3.
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.
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.
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).
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.
对于妊娠期间使用精神药物治疗，建议进行扩展治疗药物监测以进行个体化治疗调整。我们测量了母体血清、羊水和脐血中的文拉法辛（VEN）、O-去甲文拉法辛（ODV）和活性代谢物 AM（VEN+ODV 的总和）浓度。
在分娩时测量了 9 对母婴对的 VEN、ODVEN 和 AM 浓度；在 5 例中，获得了羊水样本。浓度以中位数、第一（Q1）和第三（Q3）四分位数和范围报告。通过将 VEN、ODVEN 和 AM 在羊水和脐血中的浓度除以母体血清浓度来计算渗透比。
文拉法辛的中位日剂量为 75 毫克（范围 37.5-225 毫克）。每日剂量与母体血清、脐血和羊水浓度之间没有显著相关性。中位数渗透比进入羊水为 2.5（范围 0.56-4.48）。中位数渗透比进入胎儿循环为 1.05（范围 0.62-2.08）。AM 的中位数浓度为 223.8ng/mL，范围 33.9-338.0ng/mL（母体血清），789.0ng/mL，范围 309-1052.5ng/mL（羊水）和 291.0ng/mL，范围 21.1-448.4ng/mL（脐血）。
母体血清、羊水和脐血中的 VEN、ODVEN 和 AM 浓度表明，胎儿在整个孕期可能暴露于相对较高的浓度中。羊水中的高浓度表明渗透进入和/或在羊水中积累增加，以及从羊水中消除减少。这些发现表明，与其他抗抑郁药相比，胎儿在子宫内暴露于文拉法辛的程度更高。
