Gerontology and Geriatric Research Laboratory, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
J Nephrol. 2012;25 Suppl 19:S38-47. doi: 10.5301/jn.5000137.
The prevalence of therapeutic failures (TFs) and adverse drug reactions (ADRs) markedly increased in older subjects. However, both TFs and ADRs did not always appear related to the presence of multiple pharmacologic treatments, a common status in subjects aged 65 and over. Instead, they seem more related to variations in the genes encoding protein metabolizing and transporting drugs. Thus, variations in these proteins may account for the inter-individual differences observed in drug efficacy, including the most severe clinical consequences TFs and ADRs. The genetics of drug metabolizing enzymes (DMEs) and drug transporters (DTs) is a very active area of multidisciplinary research, overlapping the fields of medicine, biology, pharmacology, and genetics. These proteins are virtually responsible for metabolism and disposition, and thus the efficacy, of a number of drugs currently used in clinical practice. This article explored some basic concepts of the pharmacogenetics of DMEs and DTs. We also focused current knowledge of the genetic basis of TFs and ADRs of the most common drugs currently used in geriatric clinics. The knowledge of what we know and what we need to know is needed to advance the application of pharmacogenetics in clinical practice, in order to introduce personalized treatments for elderly people.
治疗失败（TFs）和药物不良反应（ADRs）在老年患者中明显增多。然而，TFs 和 ADRs 并不总是与多种药物治疗的存在相关，这在 65 岁及以上的患者中很常见。相反，它们似乎与编码药物代谢和转运蛋白的基因变异更相关。因此，这些蛋白的变异可能解释了药物疗效的个体间差异，包括 TFs 和 ADRs 等最严重的临床后果。药物代谢酶（DMEs）和药物转运体（DTs）的遗传学是一个非常活跃的多学科研究领域，涵盖了医学、生物学、药理学和遗传学等领域。这些蛋白实际上负责许多目前在临床实践中使用的药物的代谢和处置，因此也影响了这些药物的疗效。本文探讨了 DMEs 和 DTs 的药物遗传学的一些基本概念。我们还重点介绍了目前关于老年科常用的最常见药物的 TFs 和 ADRs 的遗传基础的知识。了解我们已经知道的和我们需要知道的，有助于推进药物遗传学在临床实践中的应用，以便为老年人引入个性化治疗。
