title: Transplacental transfer of oseltamivir and its metabolite using the human perfused placental cotyledon model.
abstract: OBJECTIVE
  Given the lack of data regarding the use of oseltamivir (Tamiflu) during pregnancy, we aimed to evaluate the placental transfer of oseltamivir phosphate and its active metabolite oseltamivir carboxylate, using the perfused placental cotyledon model.
  
  
  METHODS
  Cotyledons were coperfused with oseltamivir phosphate and oseltamivir carboxylate using the maximal concentrations described with a 75 mg, twice-daily oral dose. Main transfer parameters such as fetal transfer rate (FTR) and clearance index (CI) were assessed.
  
  
  RESULTS
  Five placentas were coperfused with oseltamivir phosphate and oseltamivir carboxylate. The median FTR of oseltamivir phosphate was 8.5% (range, 5.0-11.6%) and the median CI was 0.3 (range, 0.2-0.6). Regarding oseltamivir carboxylate transplacental transfer, the median FTR was 6.6% (range, 3.9-9.7%), whereas the median CI was 0.2 (range, 0.2-0.5).
  
  
  CONCLUSIONS
  A transplacental transfer of oseltamivir phosphate and its metabolite oseltamivir carboxylate was detected and might have clinical relevance. Clinicians should be encouraged to report oseltamivir treatment outcomes during pregnancy.
authors.affiliation: Clinical Research Unit, Institut National de la Santé et de la Recherche Médicale, Cochin Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, France. paul.berveiller@sat.aphp.fr
authors.forename: Paul
authors.initials: P
authors.lastname: Berveiller
authors.forename: Olivier
authors.initials: O
authors.lastname: Mir
authors.forename: Cécile
authors.initials: C
authors.lastname: Vinot
authors.forename: Céline
authors.initials: C
authors.lastname: Bonati
authors.forename: Patrick
authors.initials: P
authors.lastname: Duchene
authors.forename: Carole
authors.initials: C
authors.lastname: Giraud
authors.forename: Sophie
authors.initials: S
authors.lastname: Gil
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Treluyer
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D008431:Maternal-Fetal Exchange; D053139:Oseltamivir / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011355:Prodrugs / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000998:Antiviral Agents; D011355:Prodrugs; D053139:Oseltamivir; C535162:oseltamivir carboxylate