Geriatric Unit & Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, I.R.C.C.S. Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
Curr Drug Metab. 2011 Sep;12(7):621-34. doi: 10.2174/138920011796504545.
The genetics of drug metabolizing enzymes, drug transporters and drug receptors is a very active area of multidisciplinary research, overlapping the interest of medicine, biology, pharmacology and genetics. Indeed, these proteins are virtually responsible for the metabolism, disposition and efficacy of most of available drugs. Variations in the gene encoding these proteins may account for the interindividual differences observed in drug efficacy, including severe clinical consequences such as therapeutic failures and adverse drug reactions. It is well known that the prevalence of both therapeutic failures and adverse drug reactions strongly increased in older subjects, and this did not seem to be always related to the presence of multiple pharmacological treatments, a common status in subjects aged 65 years and over. The present article explored some basic concepts of human genetics that may have important implications in the pharmacogenetics of drug metabolizing enzymes, drug transporters and receptors. We also focus the current knowledge on the genetic basis of the efficacy and the adverse drug reactions of the most common drugs used in the geriatric patient. Thus we explore the status of what we know and what we need to know to forward the application of pharmacogenetics in clinical practice, in order to introduce a personalized treatment project for the older people.
药物代谢酶、药物转运体和药物受体的遗传学是一个非常活跃的多学科研究领域，涉及医学、生物学、药理学和遗传学的交叉兴趣。事实上，这些蛋白质几乎负责大多数现有药物的代谢、处置和疗效。编码这些蛋白质的基因的变异可能导致药物疗效的个体间差异，包括严重的临床后果，如治疗失败和药物不良反应。众所周知，治疗失败和药物不良反应的发生率在老年患者中明显增加，而且这似乎并不总是与多种药物治疗同时存在有关，这在 65 岁及以上的患者中很常见。本文探讨了一些可能对药物代谢酶、药物转运体和受体的药物遗传学具有重要意义的人类遗传学基本概念。我们还重点介绍了目前关于最常用于老年患者的药物疗效和药物不良反应的遗传基础的知识。因此，我们探讨了我们所知和需要知道的以推进药物遗传学在临床实践中的应用的现状，以便为老年人引入个性化的治疗方案。
