University of Oulu, Institute of Biomedicine, Department of Pharmacology and Toxicology, Oulu, Finland.
Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1483-99. doi: 10.1517/17425250903304049.
Transporter proteins and xenobiotic metabolizing enzymes have a crucial role in the fate of xenobiotics in human body. The expression in human placenta and fetal tissues of the proteins most commonly participating in pharmaco/toxicokinetics is reviewed. In case human data are not available, relevant animal data are included. Among transporter proteins ABC transporters, monoamine transporters and organic anion transporters are pharmacologically and toxicologically of main interest. From xenobiotic enzymes, both CYP enzymes and transferases are expressed in fetal liver already during pregnancy. In the placenta, the variety of enzymes is much more restricted. During development dynamic changes occur in both xenobiotic metabolizing enzymes and drug transporters. Although the knowledge has increased substantially over the past years it is apparent from the literature that there are uncharacterized areas, especially regarding developmental expression patterns and regulation of transporters in fetal tissues and placenta. Knowledge about tissue-specific distribution and functional significance will aid our understanding of the differences in drug response and risks for adverse events during fetal development.
转运蛋白和外源化学物代谢酶在外源化学物在人体内的命运中起着至关重要的作用。本文综述了参与药物代谢动力学/毒代动力学的最常见蛋白在人胎盘和胎儿组织中的表达。在没有人体数据的情况下，还包括了相关的动物数据。在转运蛋白中，ABC 转运蛋白、单胺转运蛋白和有机阴离子转运蛋白在药理学和毒理学上具有主要意义。在外源化学物酶中，CYP 酶和转移酶在妊娠期间已经在胎肝中表达。在胎盘，酶的种类要受到更多限制。在发育过程中，外源化学物代谢酶和药物转运体都发生动态变化。尽管近年来知识有了很大的增长，但从文献中可以明显看出，仍有一些未被描述的领域，特别是关于胎儿组织和胎盘中转运体的发育表达模式和调控。关于组织特异性分布和功能意义的知识将有助于我们理解在胎儿发育过程中药物反应和不良反应风险的差异。
