The metabolism and transplacental transfer of oseltamivir in the ex vivo human model

Infect Dis Obstet Gynecol. 2008;2008:927574. doi: 10.1155/2008/927574.

Abstract

Oseltamivir phosphate is extensively metabolized in the ex vivo human placenta model, and the transplacental passage of the metabolite oseltamivir carboxylate is incomplete.

Objective: To evaluate the metabolism and transplacental transfer of oseltamivir (Tamiflu) in the ex vivo human placental model.

Study design: Perfusion studies were performed in six placentas from term, uncomplicated deliveries. Concentrations of oseltamivir phosphate (OP) that were 5-6 fold, 20-30 fold, and 600-800 fold above the therapeutic peak were tested, as neither OP nor its active metabolite, oseltamivir carboxylate (OC), could be detected at near-therapeutic concentrations. The transplacental transfer and accumulation of OC were assessed using the (14)C antipyrine reference method.

Results: OP was extensively metabolized to OC. In the 4 placentas with the highest concentration of OP, OC had a mean clearance index of 0.13 +/- 0.08, suggesting that transplacental passage occurs at a relatively low rate. Measurable fetal accumulation occurred in the two placentas with the highest initial concentrations.

Conclusions: Oseltamivir phosphate was extensively metabolized in the ex vivo model. Transplacental transfer of the metabolite was incomplete and accumulation was minimal.

MeSH terms

  • Antipyrine / metabolism
  • Antiviral Agents / analysis
  • Antiviral Agents / metabolism*
  • Antiviral Agents / pharmacokinetics
  • Female
  • Fetus / metabolism
  • Humans
  • Maternal-Fetal Exchange
  • Models, Biological
  • Oseltamivir / analysis
  • Oseltamivir / metabolism*
  • Oseltamivir / pharmacokinetics
  • Perfusion
  • Placenta / metabolism*
  • Pregnancy

Substances

  • Antiviral Agents
  • Oseltamivir
  • Antipyrine