Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
Department of Laboratory Medicine, Radboud university medical center, Nijmegen, The Netherlands.
Eur J Pharm Sci. 2018 Jul 1;119:244-248. doi: 10.1016/j.ejps.2018.04.017. Epub 2018 Apr 12.
Currently, tacrolimus is the most potent immunosuppressive agent for renal transplant recipients and is commonly prescribed during pregnancy. As data on placental exposure and transfer are limited, we studied tacrolimus placental handling in samples obtained from renal transplant recipients. We found transfer to venous umbilical cord blood, but particularly noted a strong placental accumulation. In patient samples, tissue concentrations in a range of 55-82 ng/g were found. More detailed ex vivo dual-side perfusions of term placentas from healthy women revealed a tissue-to-maternal perfusate concentration ratio of 113 ± 49 (mean ± SEM), underlining the placental accumulation found in vivo. During the 3 h ex vivo perfusion interval no placental transfer to the fetal circulation was observed. In addition, we found a non-homogeneous distribution of tacrolimus across the perfused cotyledons. In conclusion, we observed extensive accumulation of tacrolimus in placental tissue. This warrants further studies into potential effects on placental function and immune cells of the placenta.
目前，他克莫司是肾移植受者最有效的免疫抑制剂，在怀孕期间通常会开这种药。由于关于胎盘暴露和转移的数据有限，我们研究了肾移植受者样本中的他克莫司胎盘处理情况。我们发现它可以转移到静脉脐血中，但特别注意到胎盘有很强的蓄积。在患者样本中，发现组织浓度在 55-82ng/g 范围内。对来自健康女性的足月胎盘进行更详细的双面离体双侧灌注显示，组织与母体灌注液的浓度比为 113±49（平均值±SEM），这强调了体内发现的胎盘蓄积。在 3 小时的离体灌注间隔期间，没有观察到胎盘向胎儿循环的转移。此外，我们发现他克莫司在灌注的胎盘小叶中分布不均匀。总之，我们观察到他克莫司在胎盘组织中大量蓄积。这需要进一步研究对胎盘功能和胎盘免疫细胞的潜在影响。
