Koren Gideon, Ornoy Asher
a Institute of Research and Innovation , Maccabi Health Services , Israel.
b Department of Pediatrics , Hebrew University , Israel.
Expert Rev Clin Pharmacol. 2018 Apr;11(4):373-385. doi: 10.1080/17512433.2018.1425615. Epub 2018 Jan 16.
It was assumed for decades that the human placenta serves as a barrier, protecting the fetus from exposure to xenobiotics circulating in the mother. The thalidomide disaster completely reversed this concept. The study of the human placenta is therefore critical to understanding the mechanisms by which xenobiotics reach the fetus and exert their effects. Areas covered: This review describes mechanisms by which drugs interact with the human placenta, and experimental methods to study these interactions in humans. We have selected three areas of current clinical interest, where the placenta exhibits critical role in drug transport: The ABC transporters, the placental handling of cancer therapeutic drugs and the interaction between the placenta and immunoglobulins. Expert commentary: The optimal model to predict drug transfer and transport from the mother to the fetus is the isolated human placental lobule perfused in vitro. Unlike subcellular preparations or tissue homogenates, data obtained from a perfused intact tissue, where structural integrity and cell-cell organization are maintained, more closely reflect the in vivo situation. Moreover, confounding metabolic and physiologic influences are minimized and the experimental conditions can be controlled. It is important to remember that due to significant differences in the function of the placenta in the first two months (histiotrophic nutrition) and later in pregnancy (hemotrophic nutrition) there might be differences in the transplacental transfer of drugs. While most of our knowledge comes from studies on term placentae, we are in need of studies on young placenta that functions during the period of organogenesis.
几十年来，人们一直认为人类胎盘起着屏障作用，保护胎儿免受母体循环中异源生物的影响。沙利度胺灾难彻底颠覆了这一观念。因此，对人类胎盘的研究对于理解异源生物到达胎儿并发挥作用的机制至关重要。涵盖领域：本综述描述了药物与人类胎盘相互作用的机制，以及在人体中研究这些相互作用的实验方法。我们选择了当前临床关注的三个领域，胎盘在其中的药物转运中发挥关键作用：ABC转运蛋白、癌症治疗药物的胎盘处理以及胎盘与免疫球蛋白之间的相互作用。专家评论：预测药物从母体向胎儿转移和转运的最佳模型是体外灌注的分离人胎盘小叶。与亚细胞制剂或组织匀浆不同，从灌注完整组织获得的数据，其中结构完整性和细胞间组织得以维持，更能紧密反映体内情况。此外，混杂的代谢和生理影响被最小化，实验条件可以得到控制。重要的是要记住，由于胎盘在前两个月（组织营养）和妊娠后期（血液营养）的功能存在显著差异，药物的经胎盘转运可能会有所不同。虽然我们的大部分知识来自对足月胎盘的研究，但我们需要对器官形成期发挥功能的年轻胎盘进行研究。
