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Transfer of metformin across the dually perfused human placental lobule

      Objective

      Determine the kinetic parameters for the transfer of metformin (MT) across human placentas obtained from healthy pregnancies and patients with gestational diabetes.

      Study design

      The technique of dual perfusion of placental lobule was utilized in two configurations; Closed-Closed (C/C, re-circulating) or Open-Open (O/O, steady state conditions). MT was transfused at its highest reported concentration in the circulation (5g/ml) together with its [3H]-isotope. Samples from the tissue, maternal and fetal circuits (MC&FC) were collected and analyzed for MT concentration by liquid scintillation spectrometry. The kinetic parameters determined were: Fetal transfer rate (TRf), clearance (CL) and clearance index (Clindex, CL for MT/CL for antipyrine).

      Results

      Transfer of metformin across healthy and diabetic placentas in (O/O) system.There is no significant difference in TRf and CL of MT between healthy and diabetic placentas. The ratio for MT concentration in FC/MC, at the end of its transfusion in C/C system, was 0.43 ± 0.14 indicates relatively high transfer.

      Conclusion

      1. Metformin diffuses readily across human placenta from the MC to the FC. 2- Transplacental transfer of metformin is not affected by GD. 3- The low binding of metformin to proteins could explain it´s higher, than glyburide, transfer to the FC. Supported by the Obstetrical Pharmacology Research Network (OPRU/NICHD).
      Tabled 1Transfer of metformin across “healthy” and “diabetic” placentas (O/O) system
      “Healthy”“Diabetic”
      ParametersAPMetforminAPMetformin
      TRf (%)26.8 ± 3.513.4 ± 3.528.5 ± 4.014.2 ± 2.4
      CL (ml/min)0.77 ± 0.10.35 ± 0.110.86 ± 0.270.34 ± 0.06
      C1 index0.49 ± 0.10.5 ± 0.06
      Tissue retention (ugmetformin/grtissue)2.25 ± 0.031.36 ± 0.1