Mooij Miriam G, Nies Anne T, Knibbe Catherijne A J, Schaeffeler Elke, Tibboel Dick, Schwab Matthias, de Wildt Saskia N
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Room Sp-3458, Wytemaweg 80, PO-box 2060, 3000 CB, Rotterdam, The Netherlands.
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Clin Pharmacokinet. 2016 May;55(5):507-24. doi: 10.1007/s40262-015-0328-5.
Membrane transporters play an essential role in the transport of endogenous and exogenous compounds, and consequently they mediate the uptake, distribution, and excretion of many drugs. The clinical relevance of transporters in drug disposition and their effect in adults have been shown in drug-drug interaction and pharmacogenomic studies. Little is known, however, about the ontogeny of human membrane transporters and their roles in pediatric pharmacotherapy. As they are involved in the transport of endogenous substrates, growth and development may be important determinants of their expression and activity. This review presents an overview of our current knowledge on human membrane transporters in pediatric drug disposition and effect. Existing pharmacokinetic and pharmacogenetic data on membrane substrate drugs frequently used in children are presented and related, where possible, to existing ex vivo data, providing a basis for developmental patterns for individual human membrane transporters. As data for individual transporters are currently still scarce, there is a striking information gap regarding the role of human membrane transporters in drug therapy in children.
膜转运蛋白在内源性和外源性化合物的转运中起着至关重要的作用，因此它们介导了许多药物的吸收、分布和排泄。转运蛋白在药物处置中的临床相关性及其在成人中的作用已在药物相互作用和药物基因组学研究中得到证实。然而，关于人类膜转运蛋白的个体发育及其在儿科药物治疗中的作用，我们所知甚少。由于它们参与内源性底物的转运，生长和发育可能是其表达和活性的重要决定因素。本综述概述了我们目前对儿科药物处置和效应中人类膜转运蛋白的认识。文中呈现了儿童常用膜底物药物的现有药代动力学和药物遗传学数据，并在可能的情况下与现有体外数据相关联，为个体人类膜转运蛋白的发育模式提供了依据。由于目前关于个体转运蛋白的数据仍然稀缺，在人类膜转运蛋白在儿童药物治疗中的作用方面存在显著的信息空白。
