Vesell E S
Department of Pharmacology, Pennsylvania State University, College of Medicine, Hershey 17033, USA.
J Clin Pharmacol. 2000 Sep;40(9):930-8. doi: 10.1177/00912700022009666.
Large differences among normal human subjects in the efficacy and safety of many therapeutic agents are caused by genetically controlled polymorphisms of drug-metabolizing enzymes, drug transporters, and drug receptors. Development of pharmacogenomics as a new field has accelerated progress in pharmacogenetics by elucidating at the level of the human genome the inherited basis for those large interindividual variations. Examples discussed in this review illustrate how this approach can be used not only to guide new drug discovery but also to individualize therapy. Adverse drug reactions, often attributable to large differences among subjects in drug response, constitute a leading cause of death in the USA. Such high morbidity and mortality could be reduced by application of the principles of pharmacogenetics and pharmacogenomics, defined broadly as the study of genetically caused variability in drug response.
许多治疗药物在正常人类受试者中的疗效和安全性存在很大差异，这是由药物代谢酶、药物转运体和药物受体的基因控制多态性引起的。药物基因组学作为一个新领域的发展，通过在人类基因组水平上阐明这些个体间巨大差异的遗传基础，加速了药物遗传学的进展。本综述中讨论的例子说明了这种方法不仅可用于指导新药研发，还可实现个体化治疗。药物不良反应往往归因于受试者在药物反应上的巨大差异，在美国，它是导致死亡的主要原因之一。应用药物遗传学和药物基因组学原理（广义上定义为对药物反应中基因引起的变异性的研究），可以降低这种高发病率和死亡率。
