The role of organic cation transporters (OCTs) in the transfer of metformin in the dually perfused human placenta.
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.
Tertti
Kristiina
K
Department of Obstetrics and Gynecology, Turku University Hospital, Kiinamyllynkatu 4-8, FIN-20521, Turku, Finland. kristiina.tertti@tyks.fi
Ekblad
Ulla
U
Heikkinen
Tuija
T
Rahi
Melissa
M
Rönnemaa
Tapani
T
Laine
Kari
K
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
D027701:Organic Cation Transport Proteins; D002927:Cimetidine; D008687:Metformin; D000983:Antipyrine