An update on placental drug transport and its relevance to fetal drug exposure.
An update on placental drug transport and its relevance to fetal drug exposure.
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DOI：
10.1515/mr-2022-0025
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发表时间：
2022-10
期刊：
影响因子：
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通讯作者：
Chen, Xin
中科院分区：
文献类型：
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作者：
Mao, Qingcheng;Chen, Xin
孕妇往往患有需要药物治疗的疾病。大多数孕妇服用的药物都是标签外的，没有必要的剂量，疗效和安全性信息。了解药物通过胎盘屏障的转移对于了解胎儿药物暴露以及药物对胎儿的安全性和有效性至关重要。胎盘中表达的转运蛋白，包括三磷酸腺苷（ATP）结合盒外排转运蛋白和溶质载体摄取转运蛋白，在决定药物通过胎盘屏障转移，导致胎儿暴露于药物中发挥重要作用。在这篇综述中，我们提供了一个更新胎盘药物转运，包括在体外细胞/组织，离体人胎盘灌注，并在体内动物研究，可用于确定药物转运蛋白的表达和功能的胎盘以及胎盘药物转移和胎儿药物暴露。我们还描述了如何通过被动扩散或主动运输胎盘药物转移的知识可以结合生理学为基础的药代动力学建模和模拟，以预测全身胎儿药物暴露。最后，我们强调了在研究胎盘药物转运和预测胎儿药物暴露方面的知识空白，并讨论了未来的研究方向，以填补这些空白。
Pregnant women are often complicated with diseases that require treatment with medication. Most drugs administered to pregnant women are off-label without the necessary dose, efficacy, and safety information. Knowledge concerning drug transfer across the placental barrier is essential for understanding fetal drug exposure and hence drug safety and efficacy to the fetus. Transporters expressed in the placenta, including adenosine triphosphate (ATP)-binding cassette efflux transporters and solute carrier uptake transporters, play important roles in determining drug transfer across the placental barrier, leading to fetal exposure to the drugs. In this review, we provide an update on placental drug transport, including in vitro cell/tissue, ex vivo human placenta perfusion, and in vivo animal studies that can be used to determine the expression and function of drug transporters in the placenta as well as placental drug transfer and fetal drug exposure. We also describe how the knowledge of placental drug transfer through passive diffusion or active transport can be combined with physiologically based pharmacokinetic modeling and simulation to predict systemic fetal drug exposure. Finally, we highlight knowledge gaps in studying placental drug transport and predicting fetal drug exposure and discuss future research directions to fill these gaps.