Clinical Data Science Department, Japan Development Center, Pharmaceutical Development Division, Takeda Pharmaceutical Company Ltd., Osaka, Japan.
Drug Metab Pharmacokinet. 2012;27(1):2-8. doi: 10.2133/dmpk.dmpk-11-rv-093. Epub 2012 Jan 3.
Over the last two decades, identification of polymorphisms that influence human diseases has begun to have an impact on the provision of medical care. The promise of genetics lies in its ability to provide insight into an individual's susceptibility to disease, the likely nature of the disease and the most appropriate therapy. For much of its history, pharmacogenomics (PGx) has been limited to relatively simple phenotypes such as plasma drug levels. Progress in genetic technologies has broadened the scope of exploratory PGx and its implementation into safety and efficacy studies, impacting a broad spectrum of drug discovery and development activities. Recent PGx data show the ability of this approach to generate information that can be applied to target selection, dose selection, efficacy determination and safety issues. This in turn will lead to significant opportunities to influence the approaches to drug discovery, clinical development and the probability of success. In particular, adverse drug reactions are critical issues for pharmaceutical companies and for the patients who will benefit from these new medicines. In this review, we outline current progress in PGx, using examples to highlight the influence of polymorphisms, and discuss contemporary challenges for both researchers and clinicians.
在过去的二十年中，鉴定影响人类疾病的多态性开始对医疗保健的提供产生影响。遗传学的承诺在于它能够深入了解个体对疾病的易感性、疾病的可能性质和最合适的治疗方法。在其历史的大部分时间里，药物基因组学 (PGx) 一直局限于相对简单的表型，如血浆药物水平。遗传技术的进步拓宽了探索性 PGx 的范围及其在安全性和功效研究中的实施，影响了广泛的药物发现和开发活动。最近的 PGx 数据表明，这种方法有能力生成可应用于目标选择、剂量选择、疗效确定和安全性问题的信息。这反过来又将为影响药物发现、临床开发和成功概率的方法提供重要机会。特别是，药物不良反应是制药公司和将从这些新药中受益的患者的关键问题。在这篇综述中，我们概述了 PGx 的当前进展，并用实例强调了多态性的影响，并讨论了研究人员和临床医生面临的当代挑战。
