Quantitative prediction of fetal plasma concentration of fluvoxamine during dosage-tapering to the mother

Sayo Matsuoka, Satoko Hori, Hiroki Satoh, Takeshi Nagamatsu, Tomoyuki Fujii, Yasufumi Sawada

Research output: Contribution to journalArticle

Abstract

Introduction Although selective serotonin reuptake inhibitors have been used during pregnancy for the treatment of depression and anxiety disorders, the fetal plasma concentration profiles of them remained unclear. Therefore, the aim of this study was to develop a pharmacokinetic model to estimate fetal plasma concentration profiles of fluvoxamine, and to clarify the differences with those of paroxetine. Methods Perfusion studies using human placentae obtained from full-term pregnant women were conducted to estimate transplacental pharmacokinetic parameters for fluvoxamine. The characteristics of placental permeability were compared with those of paroxetine in our previous report. Using a developed model and these parameters, fetal plasma concentration profiles of fluvoxamine administered to mothers were simulated. Results The results of perfusion studies and transplacental transfer kinetic parameters indicated that fluvoxamine is less efficiently distributed to placental tissue than paroxetine. The model predicted a maternal-fetal plasma concentration ratio of 0.376 after repeated maternal administration of fluvoxamine, similar to the ratio for paroxetine. However, if the mother ceased taking drug, the model predicted a half-life of fluvoxamine in fetal plasma of 35 h, which is longer than that of paroxetine (10 h). We used the model to evaluate a proposed taper regimen for full-term pregnant women taking fluvoxamine that would minimize the risk of neonatal withdrawal syndrome. Discussion The obtained parameters and developed model enabled us to predict the fetal plasma concentration profiles of fluvoxamine. The risk of neonatal withdrawal syndrome due to abrupt discontinuation may be less with fluvoxamine than with paroxetine.

Original languageEnglish
Pages (from-to)74-81
Number of pages8
JournalPlacenta
Volume58
DOIs
Publication statusPublished - 2017 Oct

Keywords

  • Fluvoxamine
  • Human placental perfusion
  • Neonatal withdrawal syndrome
  • Paroxetine
  • Serotonin selective reuptake inhibitor
  • Transplacental transfer

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynaecology
  • Developmental Biology

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