Determination of metformin transfer across the human placenta using a dually perfused ex vivo placental cotyledon model

Objective: The aim of the study was to quantify and characterize metformin transfer across the human placenta using an ex vivo placental perfusion model. Study design: Placentas were obtained from vaginal deliveries or caesarean sections and selected cotyledons were cannulated and dually perfused. Metformin (1 μg/ml) and a permeability reference marker, antipyrine (50 μg/ml), were added to the maternal circulation. Each perfusion experiment was conducted for 180 min while samples were taken from the maternal and fetal compartments. The integrity and viability of the placenta were determined by measuring the flow rates, fetal artery inflow pressure, and hCG production during the experiments. Results: Six complete experimental set-ups were completed. The maternal-fetal transport rates for metformin and antipyrine were 10.61 ± 2.85% and 30.98 ± 5.62%, respectively. The clearance index, calculated as the ratio between the permeabilities of metformin and antipyrine, was 0.34 ± 0.05. Conclusion: The results indicate that metformin is able to cross the mature human placenta; thus, fetal exposure must be considered when treating pregnant women with metformin.