The role of organic cation transporters (OCTs) in the transfer of metformin in the dually perfused human placenta

Objectives: 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).

Study design: 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.