Objective: Glargine treatment during pregnancy does not appear to be associated with neonatal morbidity, yet the rate and extent of its passage through human placenta is unknown. The aim of the study was to quantify and characterize glargine transfer across the placenta using the ex-vivo placental perfusion model.
Methods: Placentas were obtained from vaginal deliveries or caesarean sections and selected cotyledons were cannulated and dually perfused. Glargine , 50mU/L (n=2) and 200 mU/L (n=1), and a permeability reference marker, antipyrine (50mgr/ml), were added to the maternal circulation. Each perfusion experiment was conducted for 180 minutes while samples were taken from maternal and fetal compartments.
Results: Glargine was not detected in the fetal compartment in any of the 3 complete experimental set-ups. In the maternal compartment the steady state concentration was about 50% lower then the starting concentration.
Conclusions: Insulin glargine does not cross the human placenta, implying its safety use during pregnancy. Reduced maternal steady state concentrations may suggest insulin uptake by the placenta, with possibly further metabolism of the drug by placental enzymes.
Authors:
Michal Kovo 1, Julio Wainstein 2, Zipora Matas 3, Simon Haroutiunian 4
Amnon Hoffman 4, Abraham Golan 1
Department of Obstetrics and Gynecology 1, Diabetes Unit 2 and Department of Biochemical and Endocrine Laboratory 3,
the E. Wolfson Medical Center, Holon, and Sackler School of Medicine, Tel Aviv University, Israel; Department of
Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel