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首页> 外文期刊>Reproductive toxicology >The transfer of 6-mercaptopurine in the dually perfused human placenta.
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The transfer of 6-mercaptopurine in the dually perfused human placenta.

机译：6-巯基嘌呤在双重灌注的人胎盘中的转移。

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摘要

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.
机译：免疫抑制剂硫唑嘌呤在怀孕中越来越多地被使用。人胎盘被认为是主要代谢物6-巯基嘌呤（6-MP）的相对屏障，并可能解释了人类缺乏公认的致畸性。这项研究的目的是确定人类胎盘如何使用人类胎盘灌注模型来限制6-MP的转移。将50 ng / ml（n = 4）和500 ng / ml（n = 3）6-MP加入母体循环后，其浓度双相下降，胎儿循环出现延迟。在平衡条件下，由于离子捕获，胎儿与母亲的浓度比> 1.0。与胎盘组织的结合和母体的药代动力学参数是限制6-MP胎盘转移的主要因素。主动转运不太可能发挥重要作用，涉及胎盘药物外排转运蛋白的药物相互作用或其中的多态性不太可能使胎儿面临更高的6-MP暴露风险。

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