Genetic polymorphisms in placental transporters: implications for fetal drug exposure to oral antidiabetic agents

Expert Opin Drug Metab Toxicol. 2011 Mar;7(3):325-39. doi: 10.1517/17425255.2011.553188. Epub 2011 Jan 20.

Abstract

Introduction: The prevalence of diabetes among women of childbearing age is increasing. This will inevitably increase the number of pregnancies complicated by diabetes. The management of diabetes mellitus often necessitates the use of oral antidiabetic drugs including biguanides, sulfonylureas, metiglinide analogs and thiazolidinediones. However, a significant concern with the use of these agents in pregnancy is the potential for developmental toxicity. Various antidiabetic drugs have been identified as substrates for transporters present in the syncytiotrophoblast. Therefore, the extent of transfer and fetal exposure to oral antidiabetic drugs used in pregnancy may be altered by polymorphisms in genes encoding these transport proteins.

Areas covered: This review covers current research examining genetic polymorphisms in transporters expressed in the syncytiotrophoblast and evidence supporting the involvement of these transporters in the transport of oral antidiabetic agents. The aim is to provide insight into how the transfer of antidiabetic drugs across the placental trophoblast may be altered by polymorphisms in drug transporters.

Expert opinion: There is a paucity of studies examining the influence of polymorphisms on transporter activity in the placenta and how the transfer of oral antidiabetics may be altered. Further research employing in vivo models is required to allow for the prediction of the potential consequences of polymorphisms on placental transporter expression and function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / metabolism*
  • Maternal-Fetal Exchange / physiology*
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism*
  • Placenta / metabolism*
  • Polymorphism, Single Nucleotide / physiology*
  • Pregnancy

Substances

  • Hypoglycemic Agents
  • Membrane Transport Proteins