关键词: Drug transfer Ex vivo perfusion Fetal exposure Placental perfusion Standardization

来  源:   DOI:10.1016/j.placenta.2024.03.007

Abstract:
The ex vivo human placenta perfusion model has proven to be clinically relevant to study transfer- and fetal exposure of various drugs. Although the method has existed for a long period, the setup of the perfusion model has not been generalized yet. This review aims to summarize the setups of ex vivo placental perfusion models used to examine drug transfer across the placenta to identify generalized properties and differences across setups. A literature search was carried out in PubMed September 26, 2022. Studies were labeled as relevant when information was reported, between 2000 and 2022, on the setups of ex vivo placental perfusion models used to study drug transfer across the placenta. The placenta perfusion process, and the data extraction, was divided into phases of preparation, control, drug, and experimental reflecting the chronological timeline of the different phases during the entire placental perfusion process. 135 studies describing an ex vivo human placental perfusion experiment were included. Among included studies, the majority (78.5%) analyzed drug perfusion in maternal to fetal direction, 18% evaluated bi-directional drug perfusion, 3% under equilibrium conditions, and one study investigated drug perfusion in fetal to maternal direction. This literature review facilitates the comparison of studies that employ similar placenta perfusion protocols for drug transfer studies and reveals significant disparities in the setup of these ex vivo placental perfusion models. Due to interlaboratory variability, perfusion studies are not readily comparable or interchangeable. Therefore, a stepwise protocol with multiple checkpoints for validating placental perfusion is needed.
摘要:
体外人胎盘灌注模型已被证明与研究各种药物的转移和胎儿暴露临床相关。虽然这种方法已经存在了很长时间,灌注模型的设置尚未得到推广。这篇综述旨在总结离体胎盘灌注模型的设置,该模型用于检查整个胎盘的药物转移,以确定不同设置的广义特性和差异。2022年9月26日在PubMed进行了文献检索。报告信息时,研究被标记为相关,在2000年至2022年之间,建立了用于研究药物跨胎盘转移的离体胎盘灌注模型。胎盘灌注过程,和数据提取,分为准备阶段,control,药物,和实验反映了整个胎盘灌注过程中不同阶段的时间顺序。包括描述离体人胎盘灌注实验的135项研究。在纳入的研究中,大多数(78.5%)分析了从母体到胎儿方向的药物灌注,18%评价双向药物灌注,在平衡条件下3%,一项研究调查了胎儿到母体方向的药物灌注。该文献综述促进了采用类似胎盘灌注方案进行药物转移研究的研究的比较,并揭示了这些离体胎盘灌注模型的建立中的显着差异。由于实验室间的差异,灌注研究不容易比较或可互换。因此,需要有多个检查点的逐步方案来验证胎盘灌注.
公众号