title: The transfer of 6-mercaptopurine in the dually perfused human placenta.
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.
authors: Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada.
authors: J R
authors: JR
authors: Hutson
authors: A
authors: A
authors: Lubetsky
authors: A
authors: A
authors: Walfisch
authors: B G
authors: BG
authors: Ballios
authors: F
authors: F
authors: Garcia-Bournissen
authors: G
authors: G
authors: Koren
mesh_terms: D000983:Antipyrine / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D015122:Mercaptopurine / Q000378:metabolism*; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D015122:Mercaptopurine; D000983:Antipyrine