Behravan Javad, Piquette-Miller Micheline
University of Toronto, Department of Pharmaceutical Sciences, 144 College Street, Toronto, Ontario, M5S 3M2, Canada.
Expert Opin Drug Metab Toxicol. 2007 Dec;3(6):819-30. doi: 10.1517/17425255.3.6.819.
The placenta serves an important role both as a protective barrier as well as in normal fetal development. The ATP-binding cassette (ABC) proteins perform crucial functions in the distribution of nutrients and exchange of waste metabolites across the placenta. They also protect the developing fetus from xenobiotics to which the pregnant mother is exposed. Recent studies in P-glycoprotein (P-gp) deficient mdr1a and mdr1b (-/-) CF-1 mice have shown pronounced increases in fetal exposure to P-gp substrates due to increased transplacental penetration demonstrating the important protective role of P-gp to the developing fetus. The role of placental ABC transporter proteins in protecting the fetus against maternal exposure to drugs, toxins and other xenobiotics is discussed. Overall, the paucity of information available on the transplacental transfer of drugs emphasizes the need to further employ preclinical in vivo models for drug development in order to best predict fetal outcomes of drug administration to pregnant mothers.
胎盘在作为保护屏障以及胎儿正常发育过程中都起着重要作用。ATP结合盒（ABC）蛋白在营养物质的分布以及胎盘内外代谢废物的交换中发挥着关键作用。它们还能保护发育中的胎儿免受母体所接触的外源性物质的影响。近期对P-糖蛋白（P-gp）缺陷的mdr1a和mdr1b（-/-）CF-1小鼠的研究表明，由于经胎盘渗透增加，胎儿对P-gp底物的暴露显著增加，这证明了P-gp对发育中胎儿的重要保护作用。本文讨论了胎盘ABC转运蛋白在保护胎儿免受母体所接触的药物、毒素和其他外源性物质影响方面的作用。总体而言，关于药物经胎盘转运的可用信息匮乏，这凸显了进一步采用临床前体内模型进行药物研发以最佳预测给怀孕母亲用药后胎儿结局的必要性。
