Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Public Health, Section of Environmental Health, University of Copenhagen, Denmark.
Placenta. 2022 May;122:29-45. doi: 10.1016/j.placenta.2022.03.128. Epub 2022 Mar 31.
At least 80% of pregnant woman in Europe use at least one medication during their pregnancy. The majority of these drugs are prescribed off-label. A better understanding of drug transport and effects in the placenta can provide an improved pharmacological basis to rationalize drug and dose selection for prescription. Here we provide a narrative review of studies that used the ex vivo placenta perfusion model to study placental drug transport and vascular effects of pharmaceuticals. For studies on placental transfer, we found that the methodology used varied substantially between studies as well as the way in which data was reported. Across the different therapeutic groups, ex vivo measurements of transfer generally corresponded well to in vivo findings. Still, further standardization of the perfusion technique would facilitate a broader use of perfusion data, e.g. in the context of quantitative systems pharmacology models as has been explored in recent years. Only few studies investigated the effects of drugs on the vascular tone using the ex vivo dual-side perfusion model. The model was particularly applied to study vasodilatory effects of pharmaceuticals in the fetoplacental circulation. In conclusion, the ex vivo dually perfused human cotyledon provides a relevant system to gain insights in placental drug disposition and study effects on the fetoplacental vasculature.
在欧洲，至少有 80%的孕妇在怀孕期间至少使用一种药物。这些药物中的大多数都是未经批准的处方用药。更好地了解药物在胎盘内的转运和作用，可以为合理选择药物和剂量提供更好的药理学基础。本文对使用离体胎盘灌注模型研究胎盘药物转运和药物对胎盘血管作用的研究进行了综述。对于胎盘转运的研究，我们发现研究之间使用的方法以及报告数据的方式有很大差异。在不同的治疗组中，离体测量的药物转运通常与体内发现的结果非常吻合。尽管如此，灌注技术的进一步标准化将有助于更广泛地使用灌注数据，例如在近年来探索的定量系统药理学模型的背景下。只有少数研究使用离体双侧灌注模型研究药物对血管张力的影响。该模型特别适用于研究药物在胎-胎盘循环中的血管扩张作用。总之，离体双侧灌注人胎盘绒毛膜提供了一个相关的系统，可以深入了解胎盘药物处置，并研究对胎-胎盘血管的影响。
