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

Kovo, Michal; Haroutiunian, Simon; Feldman, Noa; Hoffman, Amnon; Glezerman, Marek

doi:10.1016/j.ejogrb.2007.01.013

« Previous Next »European Journal of Obstetrics & Gynecology and Reproductive Biology
Volume 136, Issue 1 , Pages 29-33, January 2008

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

Michal Kovo
- Department of Obstetrics and Gynecology, the E. Wolfson Medical Center, Holon, and Sackler School of Medicine, Tel Aviv University, Israel
- These authors contributed equally to this work.
Simon Haroutiunian
- Department of Pharmaceutics, School of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel
- These authors contributed equally to this work.
Noa Feldman
- Department of Obstetrics and Gynecology, the E. Wolfson Medical Center, Holon, and Sackler School of Medicine, Tel Aviv University, Israel
Amnon Hoffman
- Department of Pharmaceutics, School of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel
- Corresponding author at: Department of Pharmaceutics, School of Pharmacy, Hebrew University of Jerusalem, P.O. Box 12065, 91120 Jerusalem, Israel. Tel.: +972 2675 7014; fax: +972 2675 7246.
Marek Glezerman
- Department of Obstetrics and Gynecology, the E. Wolfson Medical Center, Holon, and Sackler School of Medicine, Tel Aviv University, Israel

Received 13 May 2006; received in revised form 1 January 2007; accepted 9 January 2007. published online 09 March 2007.

Abstract

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 (1μg/ml) and a permeability reference marker, antipyrine (50μg/ml), were added to the maternal circulation. Each perfusion experiment was conducted for 180min 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.

Keywords: Placenta, Metformin, Ex vivo placental cotyledon model