Bhogal Nirmala, Balls Michael
FRAME, Russell & Burch House, 96-98 North Sherwood Street, Nottingham NG1 4EE, UK.
Curr Drug Discov Technol. 2008 Sep;5(3):250-62. doi: 10.2174/157016308785739839.
Despite increasing investment in drug discovery and development, only around one in every ten new medicinal products that progresses to clinical testing ever reach from the registration stage. Approximately half of all drug failures are attributed to problems with efficacy and toxicity not anticipated from preclinical studies. As a consequence, the pharmaceutical industry is adopting a much more flexible and multi-disciplinary approach to drug discovery and development. Indeed, the line between basic and applied science is constantly being eroded, not least because of the increasing sophistication of therapeutic procedures and the complexity of the diseases that they aim to treat. Here, we look at the new technologies that are being explored as a way of reducing drug attrition rates and the development of chemical drugs and biotherapeutics. Specifically, we will consider the ways in which genomics and related disciplines, engineered cell-based and microfluidics systems, and nanotechnologies are being developed and used alongside in silico platforms during early drug pharmacokinetics and toxicity studies. The way in which information from such systems biology-oriented approaches can be integrated with information from animal based preclinical safety, toxicological and pharmacological studies on investigative medicinal products is considered, in view of its current and possible impact on clinical trial design.
尽管在药物研发方面的投资不断增加，但每十种进入临床试验的新药品中，只有大约一种能够进入注册阶段。所有药物研发失败案例中，约有一半是由于临床前研究未预期到的疗效和毒性问题。因此，制药行业在药物研发方面正采用更加灵活和多学科的方法。事实上，基础科学和应用科学之间的界限正在不断被打破，这尤其是因为治疗程序日益复杂，以及它们旨在治疗的疾病的复杂性。在此，我们将探讨正在探索的新技术，作为降低药物损耗率以及化学药物和生物治疗药物研发的一种方式。具体而言，我们将考虑基因组学及相关学科、基于工程细胞的微流控系统和纳米技术在早期药物药代动力学和毒性研究中与计算机模拟平台一起被开发和使用的方式。鉴于此类面向系统生物学的方法所提供的信息对临床试验设计的当前及可能的影响，我们还将考虑如何将这些信息与基于动物的临床前安全性、毒理学和药理学研究中关于研究性药品的信息进行整合。
