title: Transplacental transfer of oseltamivir carboxylate.
abstract: OBJECTIVE
  Determine the bidirectional transfer of oseltamivir carboxylate (OC) across term human placenta and its distribution between the tissue, maternal and fetal circuits.
  
  
  METHODS
  The technique of dual perfusion of placental lobule (DPPL) in its recirculating mode was utilized to determine the transfer of the drug. OC (350 ng/mL) was co-perfused with its [(3)H]-isotope and the marker compound antipyrine (AP, 20 µg/mL) together with its [(14)C]-isotope. The concentrations of OC and any of its metabolite(s) formed during perfusion were determined in the tissue, maternal and fetal circuits by liquid scintillation spectrometry following their separation by High Performance Liquid Chromatography (HPLC).
  
  
  RESULTS
  The distribution of OC following its perfusion in the Maternal-to-Fetal direction for 4 h was as follows: 21 ± 4% of the drug was transferred to the fetal circuit, 13 ± 5% was retained by the perfused lobule, and 66 ± 4% remained in the maternal circuit. The normalized transfer of OC to that of AP (Clearance index) in the maternal-to-fetal direction was (0.47 ± 0.11) and was not different from its transfer from the fetal-to-maternal direction (0.47 ± 0.06) suggesting that involvement of placental efflux transporters is unlikely.
  
  
  CONCLUSIONS
  OC crosses human placenta. As the transfer rate of OC is 47% of the freely diffusible AP, it is likely that fetus could be exposed to OC during pregnancy.
authors.affiliation: Department of Obstetrics & Gynecology, University of Texas Medical Branch, Galveston, TX 77555-0587, USA.
authors.forename: Tatiana N
authors.initials: TN
authors.lastname: Nanovskaya
authors.forename: Svetlana
authors.initials: S
authors.lastname: Patrikeeva
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhan
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.forename: Mahmoud S
authors.initials: MS
authors.lastname: Ahmed
mesh_terms: D000998:Antiviral Agents / Q000493:pharmacokinetics; D001692:Biological Transport / Q000502:physiology; D002478:Cells, Cultured; D004058:Diffusion; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology; D009924:Organ Culture Techniques; D053139:Oseltamivir / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D047929:Term Birth / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; C535162:oseltamivir carboxylate