title: The role of organic cation transporters (OCTs) in the transfer of metformin in the dually perfused human placenta.
abstract: OBJECTIVE
  Our aim was to investigate the mode of placental transfer of metformin in term human placenta with special reference to involvement of the organic cation transporters (OCTs).
  
  
  METHODS
  Twenty-nine placentas were obtained after delivery and a 2-h non-recirculating perfusion of a single placental cotyledon was performed to study maternal-to-fetal and fetal-to-maternal transport of metformin, which is a substrate for OCTs by using antipyrine as a reference of passive diffusion transfer compound. Cimetidine was used as an inhibitor for OCT-dependent active transfer.
  
  
  RESULTS
  Maternal-to-fetal transfer of metformin and antipyrine were 3.7% and 10.0%, respectively, and fetal-to-maternal transfers were 15.5% and 42.3%, respectively. Cimetidine did not have any effect on the transfer of metformin. Fetal-to-maternal transfer of metformin was significantly higher than maternal-to-fetal transfer (P<0.05) in perfusions performed with or without cimetidine.
  
  
  CONCLUSIONS
  A higher transfer rate of metformin was detected in fetal-to-maternal than maternal-to-fetal direction, but a similar difference was observed with antipyrine. Inhibition of OCTs did not have a significant effect on the placental transfer of metformin. Although the existence of other active transporting systems cannot be ruled out, the influence of OCT-dependent active transport system on the placental pharmacokinetics of metformin is unlikely significant.
authors.affiliation: Department of Obstetrics and Gynecology, Turku University Hospital, Kiinamyllynkatu 4-8, FIN-20521, Turku, Finland. kristiina.tertti@tyks.fi
authors.forename: Kristiina
authors.initials: K
authors.lastname: Tertti
authors.forename: Ulla
authors.initials: U
authors.lastname: Ekblad
authors.forename: Tuija
authors.initials: T
authors.lastname: Heikkinen
authors.forename: Melissa
authors.initials: M
authors.lastname: Rahi
authors.forename: Tapani
authors.initials: T
authors.lastname: Rönnemaa
authors.forename: Kari
authors.initials: K
authors.lastname: Laine
mesh_terms: D000983:Antipyrine / Q000493:pharmacokinetics; D001693:Biological Transport, Active / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000502:physiology*; D008687:Metformin / Q000493:pharmacokinetics*; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D010477:Perfusion / Q000379:methods*; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy
chemical_list: D027701:Organic Cation Transport Proteins; D002927:Cimetidine; D008687:Metformin; D000983:Antipyrine