Comparative placental transport of oral hypoglycemic agents in humans: a model of human placental drug transfer

Am J Obstet Gynecol. 1994 Sep;171(3):653-60. doi: 10.1016/0002-9378(94)90078-7.


Objective: This study compares the human placental transport of glyburide, glipizide, chlorpropamide, and tolbutamide.

Study design: The recirculating single cotyledon human placenta model tested maternal-to-fetal transport in term placentas perfused immediately after delivery. Drug levels were measured by high-performance liquid chromatography and liquid scintillation spectrometry, and transport rates were calculated by comparing maternal and fetal concentrations.

Results: The transport of these substances differed significantly over a tenfold range (analysis of variance, p < 0.0008). A significant association exists by multiple linear regression between drug transfer and molecular weight, dissociation constant, and the octanol-water partition coefficient (R2 = 0.91, p < 0.0001).

Conclusions: There is significant variability in human placental transfer rates of the oral hypoglycemics, which strongly correlates with molecular properties. These data suggest that less fetal exposure may occur with second-generation sulfonylureas and anticipate that regression models may be useful in selecting agents that minimize placental transport to the fetus.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Analysis of Variance
  • Antipyrine / pharmacokinetics
  • Biological Transport / physiology
  • Chlorpropamide / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • Female
  • Glipizide / pharmacokinetics
  • Glyburide / pharmacokinetics
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacokinetics*
  • Maternal-Fetal Exchange*
  • Models, Biological*
  • Molecular Weight
  • Placenta / metabolism*
  • Pregnancy
  • Regression Analysis
  • Tolbutamide / pharmacokinetics


  • Hypoglycemic Agents
  • Tolbutamide
  • Glyburide
  • Antipyrine
  • Chlorpropamide
  • Glipizide