University of the Aegean, Department of Food Science and Nutrition, 2 Mitropoliti Ioakeim Street, Myrina, Lemnos 81400, Greece.
Expert Opin Drug Metab Toxicol. 2012 Oct;8(10):1263-75. doi: 10.1517/17425255.2012.699041. Epub 2012 Jul 11.
Placenta plays an obligatory role in fetal growth and development by performing a multitude of functions, including embryo implantation, transport of nutrients and elimination of metabolic waste products and endocrine activity. Drugs and chemicals can transfer across the placental barrier from mother to fetus either by passive diffusion mechanisms and/or via a network of active transporters, which may lead to potential fetotoxicity effects. Placenta also expresses a wide variety of enzymes, being capable of metabolizing a large diversity of drugs and chemicals to metabolites of lower or even higher toxicity than parent compounds.
The present review aims to summarize the current toxicological aspects in the emerging topic of drug transport and metabolism across the human placental barrier.
There is an emerging demand for accurate assessment of drug transport and metabolism across the human placental barrier, on the basis of a high throughput screening process in the early stages of drug design, to avoid drug candidates from potential fetotoxicity effects. In this aspect, combined studies, which take into account in vivo and in vitro investigations, as well as the ex vivo perfusion method and the recently developed computer-aided technologies, may significantly contribute to this direction.
胎盘通过执行多种功能，包括胚胎着床、营养物质的运输以及代谢废物和内分泌活性物质的清除，在胎儿生长和发育中起着必不可少的作用。药物和化学物质可以通过被动扩散机制和/或通过主动转运体网络从母体转移到胎儿，这可能导致潜在的胎儿毒性作用。胎盘还表达多种酶，能够代谢大量的药物和化学物质，将其转化为毒性比母体化合物更低甚至更高的代谢物。
本综述旨在总结在人类胎盘屏障药物转运和代谢这一新兴主题中的毒理学方面的最新进展。
在药物设计的早期阶段，基于高通量筛选过程，对药物透过胎盘屏障的转运和代谢进行准确评估的需求日益增长，以避免候选药物产生潜在的胎儿毒性作用。在这方面，结合体内和体外研究，以及最近开发的计算机辅助技术的离体灌注方法，可能会为此方向做出重大贡献。
