Investigating the potential role of multi-drug resistance protein (MRP) transporters in fetal to maternal glyburide efflux in the human placenta

J Obstet Gynaecol. 2008 Jul;28(5):485-9. doi: 10.1080/01443610802091420.

Abstract

Glyburide, a drug used to treat gestational diabetes has previously been shown not to be measurable in fetal blood, and to be transferred from the fetal to the maternal circulation against a concentration gradient. The objective of the study is to determine whether indomethacin, an inhibitor of the multi-drug resistance family (MRP) of transporters is involved in the active efflux of glyburide from the fetus to the mother. Using the dually perfused human placental cotyledon model, 12 perfusions were performed of both glyburide and indomethacin concomitantly. The rate of transfer of glyburide in the presence of inhibitor was not different from the rate of transfer of glyburide in the absence of inhibitor. Furthermore, our study suggests that MRP1, 2 or 3 may be only minimally involved in the transport of glyburide across the human placenta. These results pose other ABC transporters, such as likely candidates for the placental transfer of glyburide.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Diabetes, Gestational / drug therapy
  • Female
  • Glyburide / pharmacokinetics*
  • Glyburide / pharmacology
  • Glyburide / therapeutic use
  • Humans
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Indomethacin / pharmacokinetics*
  • Indomethacin / pharmacology
  • Male
  • Maternal-Fetal Exchange*
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Placenta / metabolism*
  • Pregnancy

Substances

  • Hypoglycemic Agents
  • Multidrug Resistance-Associated Proteins
  • Glyburide
  • Indomethacin