کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2594030 1132256 2011 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The transfer of 6-mercaptopurine in the dually perfused human placenta
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
The transfer of 6-mercaptopurine in the dually perfused human placenta
چکیده انگلیسی

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.


► We use the human placental perfusion model to investigate 6-mercaptopurine transfer.
► Placental tissue binding and maternal pharmacokinetic parameters restrict transfer.
► Active transport is unlikely to play a significant role in restricted transfer.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Reproductive Toxicology - Volume 32, Issue 3, November 2011, Pages 349–353
نویسندگان
, , , , , ,