National University of Singapore, Clinical Research Centre, Department of Pharmacology, Singapore.
Expert Opin Drug Metab Toxicol. 2009 Nov;5(11):1369-83. doi: 10.1517/17425250903176421.
It has increasingly been recognized that few molecules move across the cell membrane without the assistance of transporter proteins. Large superfamilies of transporter proteins have been identified in every living cell, including microorganisms and mitochondria. This report reviews the role of transporters in physiology and pharmacology, and identifies where this may have an impact on drug efficacy and toxicity. This new understanding will require a fresh appreciation of pharmacokinetics and drug effects, as the current paradigms are based largely on the assumption that drug molecules have a reasonable unrestricted permeability across membranes. Rather than just focusing on clearance changes and central compartment pharmacokinetics, it will become increasingly necessary to examine the peripheral tissue distribution of drugs to more accurately predict drug efficacy and toxicity.
越来越多的人认识到，几乎没有分子可以在没有转运蛋白协助的情况下穿过细胞膜。在每个活细胞中，包括微生物和线粒体，都鉴定出了大量的转运蛋白超家族。本报告综述了转运蛋白在生理学和药理学中的作用，并确定了这可能对药物疗效和毒性产生影响的地方。这种新的认识将需要对药代动力学和药物作用有新的认识，因为当前的范式主要基于药物分子在穿过膜时有合理的无限制通透性的假设。与其仅仅关注清除率的变化和中央室药代动力学，检查药物在周围组织中的分布将变得越来越必要，以便更准确地预测药物的疗效和毒性。
