Matsuoka S, et al. – Analysts develop a pharmacokinetic model to estimate fetal plasma concentration profiles of fluvoxamine and aim to explain the differences with those of paroxetine. The current study shows that the obtained parameters and developed model enabled us to predict the fetal plasma concentration profiles of fluvoxamine. The risk of neonatal withdrawal syndrome because of abrupt discontinuation may be less with fluvoxamine than with paroxetine.

Methods

• Perfusion studies utilizing human placentae obtained from full–term pregnant women were conducted to estimate transplacental pharmacokinetic parameters for fluvoxamine.
• The attributes of placental permeability were compared with those of paroxetine in the previous report.
• Utilizing a developed model and these parameters, fetal plasma concentration profiles of fluvoxamine administered to mothers were simulated.

Results

• The outcomes 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).
• They utilized the model to assess a proposed taper regimen for full–term pregnant women taking fluvoxamine that would minimize the risk of neonatal withdrawal syndrome.