The transfer of 6-mercaptopurine in the dually perfused human placenta

Reprod Toxicol. 2011 Nov;32(3):349-53. doi: 10.1016/j.reprotox.2011.08.008. Epub 2011 Aug 30.


The immunosuppressant azathioprine is increasingly being used in pregnancy. The human placenta is considered a relative barrier to the major metabolite, 6-mercaptopurine (6-MP), and likely explains the lack of proven teratogenicity in humans. The aim of this study was to determine how the human placenta restricts 6-MP transfer using the human placental perfusion model. After addition of 50 ng/ml (n=4) and 500 ng/ml (n=3) 6-MP into the maternal circulation, there was a biphasic decline in its concentration and a delay in fetal circulation appearance. Under equilibrative conditions, the fetal-to-maternal concentration ratio was >1.0 as a result of ion trapping. Binding to placental tissue and maternal pharmacokinetic parameters are the main factors that restrict placental transfer of 6-MP. Active transport is unlikely to play a significant role and drug interactions involving, or polymorphisms in, placental drug efflux transporters are not likely to put the fetus at risk of higher 6-MP exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipyrine / pharmacokinetics
  • Female
  • Humans
  • In Vitro Techniques
  • Maternal-Fetal Exchange*
  • Mercaptopurine / metabolism*
  • Perfusion
  • Placenta / metabolism*
  • Pregnancy


  • Mercaptopurine
  • Antipyrine