title: Transfer of repaglinide in the dually perfused human placenta and the role of organic anion transporting polypeptides (OATPs).
abstract: OBJECTIVE
  Our aim was to investigate the placental transfer of repaglinide by ex vivo placental perfusion experiment. In addition, the involvement of the active organic anion transporters (OATP1B1, OATP1B3 and OATP2B1) was studied by assessing the single nucleotide polymorphisms (SNPs) in genes (SLCO1B1, SLCO1B3 and SLCO2B1) encoding OATPs.
  
  
  METHODS
  Fifteen 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 repaglinide by using antipyrine as a reference of passive-diffusion transfer compound. Genotyping was performed for all placentas.
  
  
  RESULTS
  Maternal-to-fetal transfer of repaglinide and antipyrine were 1.5% and 13.2%, respectively, and fetal-to-maternal transfers were 6.7% and 40.3%, respectively. Fetal-to-maternal transfer of repaglinide was statistically significantly higher than maternal-to-fetal transfer (P<0.0001). The number of placentas was not sufficient for proper statistical analysis, but the fetal-to-maternal transfer seemed to be affected by the SLCO1B3 polymorphism.
  
  
  CONCLUSIONS
  The placental transfer of repaglinide from mother to fetus was low. Since a higher transfer rate of repaglinide was observed in fetal-to-maternal than maternal-to-fetal direction, active transport by OATP-transporters may be an important factor in fetal exposure to repaglinide.
authors.affiliation: Department of Obstetrics and Gynecology, Turku University Central Hospital, Turku, Finland. kristiina.tertti@tyks.fi
authors.forename: Kristiina
authors.initials: K
authors.lastname: Tertti
authors.forename: Aleksanteri
authors.initials: A
authors.lastname: Petsalo
authors.forename: Mikko
authors.initials: M
authors.lastname: Niemi
authors.forename: Ulla
authors.initials: U
authors.lastname: Ekblad
authors.forename: Ari
authors.initials: A
authors.lastname: Tolonen
authors.forename: Tapani
authors.initials: T
authors.lastname: Rönnemaa
authors.forename: Miia
authors.initials: M
authors.lastname: Turpeinen
authors.forename: Tuija
authors.initials: T
authors.lastname: Heikkinen
authors.forename: Kari
authors.initials: K
authors.lastname: Laine
mesh_terms: D002219:Carbamates / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics / Q000502:physiology*; D010477:Perfusion; D010880:Piperidines / Q000493:pharmacokinetics*; D010920:Placenta / Q000098:blood supply / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D053719:Tandem Mass Spectrometry
chemical_list: D002219:Carbamates; D007004:Hypoglycemic Agents; D027361:Organic Anion Transporters; D010880:Piperidines; C072379:repaglinide