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

J. R. Hutson, A. Lubetsky, A. Walfisch, B. G. Ballios, F. Garcia-Bournissen, G. Koren

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)349-353
Number of pages5
JournalReproductive Toxicology
Volume32
Issue number3
DOIs
StatePublished - 1 Nov 2011
Externally publishedYes

Keywords

  • 6-Mercaptopurine
  • Azathioprine
  • Placenta
  • Placental perfusion
  • Pregnancy

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